123 hot topic(s) found with the query "Gwas"
Including diverse populations enhances the discovery of type 2 diabetes loci
S Fatumo, Nat Rev Genetics, November 22, 2023
(Posted: Nov 22, 2023 9AM)
From the paper: "A recent multi-ancestry GWAS meta-analysis greatly advances our understanding of the genetic basis of T2D by encompassing a broad range of populations. The insights gained from this research provide a foundation for future functional investigations, therapeutic development and the translation of GWAS findings to improve global health outcomes for all, regardless of genetic background. "
Genetic risk prediction in Hispanics/Latinos: milestones, challenges, and social-ethical considerations.
Betzaida L Maldonado et al. J Community Genet 2023 11
(Posted: Nov 17, 2023 8AM)
From the abstract: "Recent efforts have focused on increasing racial and ethnic diversity in GWAS, thus, addressing some of the limitations of genetic risk prediction in these populations. Even with these efforts, few studies focus exclusively on Hispanics/Latinos. Additionally, Hispanic/Latino populations are often considered a single population despite varying admixture proportions between and within ethnic groups, diverse genetic heterogeneity, and demographic history. Combined with highly heterogeneous environmental and socioeconomic exposures, this diversity can reduce the transferability of genetic risk prediction models. "
Pragmatic Approach to Applying Polygenic Risk Scores to Diverse Populations.
Aniruddh P Patel et al. Curr Protoc 2023 11 (11) e911
(Posted: Nov 07, 2023 0PM)
From the abstract: " We present a pragmatic approach to optimize a PRS for a population of interest that leverages publicly available data and methods and consists of seven steps that are easily implemented without the requirement of expertise in complex genetics: step 1, selecting source genome-wide association studies (GWAS) and imputation; step 2, selecting methods to compute polygenic score; step 3, adjusting scores using principal components of genetic ancestry; step 4, selecting the best performing score; step 5, defining percentiles of a population distribution; step 6, validating performance of the optimized polygenic score; and step 7, implementing the optimized polygenic score in clinical practice."
A linear weighted combination of polygenic scores for a broad range of traits improves prediction of coronary heart disease.
Kristjan Norland et al. Eur J Hum Genet 2023 9
(Posted: Sep 27, 2023 8AM)
From the abstract: "Polygenic scores (PGS) for coronary heart disease (CHD) are constructed using GWAS summary statistics for CHD. However, pleiotropy is pervasive in biology and disease-associated variants often share etiologic pathways with multiple traits. Therefore, incorporating GWAS summary statistics of additional traits could improve the performance of PGS for CHD. "
Boosting the power of genome-wide association studies within and across ancestries by using polygenic scores.
Adrian I Campos et al. Nat Genet 2023 9
(Posted: Sep 20, 2023 7AM)
From the abstract: "Genome-wide association studies (GWASs) have been mostly conducted in populations of European ancestry, which currently limits the transferability of their findings to other populations. Here, we show, through theory, simulations and applications to real data, that adjustment of GWAS analyses for polygenic scores (PGSs) increases the statistical power for discovery across all ancestries. "
Genome-wide association study on pharmacological outcomes of musculoskeletal pain in UK Biobank.
Song Li et al. Pharmacogenomics J 2023 8
(Posted: Aug 18, 2023 7AM)
To investigate the genetic component of treatment outcome differences, we performed a genome-wide association study (GWAS) in ~23,000 participants with musculoskeletal pain from the UK Biobank. NSAID vs. opioid users were compared as a reflection of the treatment outcome of NSAIDs. We identified one genome-wide significant hit in chromosome 4 (rs549224715, P?=?3.88?×?10-8). Suggestive significant (P?<?1?×?10-6) loci were functionally annotated to 18 target genes, including four genes linked to neuropathic pain processes or musculoskeletal development.
Converging evidence from exome sequencing and common variants implicates target genes for osteoporosis
S Zhou et al, Nature Genetics, August 9, 2023
(Posted: Aug 09, 2023 4PM)
We undertook a large-scale multiancestry exome-wide association study for estimated bone mineral density, which showed that the burden of rare coding alleles in 19 genes was associated with estimated bone mineral density (P<3.6×10–7). These genes were highly enriched for a set of known causal genes for osteoporosis (65-fold; P=2.5×10–5). Exome-wide significant genes had 96-fold increased odds of being the top ranked effector gene at a given GWAS locus (P=1.8×10–10). By integrating proteomics Mendelian randomization evidence, we prioritized CD109 (cluster of differentiation 109) as a gene for which heterozygous loss of function is associated with higher bone density.
Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms.
Xin Wang et al. Circ Genom Precis Med 2023 6 e003808
(Posted: Jun 09, 2023 7AM)
We applied a validated ECG-AI model for predicting incident AF to ECGs from 39 986 UK Biobank participants without AF. We then performed a genome-wide association study (GWAS) of the predicted AF risk and compared it with an AF GWAS and a GWAS of risk estimates from a clinical variable model.
In the ECG-AI GWAS, we identified 3 signals (P<5×10-8) at established AF susceptibility loci marked by the sarcomeric gene TTN and sodium channel genes SCN5A and SCN10A. Predicted AF risk from an ECG-AI model is influenced by genetic variation implicating sarcomeric, ion channel and body height pathways. ECG-AI models may identify individuals at risk for disease via specific biological pathways.
GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19
EP Castineira et al, Nature, May 17, 2023
(Posted: May 17, 2023 0PM)
Here we analyze 24,202 cases of COVID-19 with critical illness comprising a combination of microarray genotype and whole-genome sequencing data from cases of critical illness in the international GenOMICC (11,440 cases) study, combined with other studies recruiting hospitalized patients with a strong focus on severe and critical disease: ISARIC4C (676 cases) and the SCOURGE consortium (5,934 cases). To put these results in the context of existing work, we conduct a meta-analysis of the new GenOMICC genome-wide association study (GWAS) results with previously published data. We find 49 genome-wide significant associations, of which 16 have not been reported previously.
Genetic and Clinical Determinants of Telomere Length
P Allaire et al, HGG Advances, April 2023
(Posted: May 03, 2023 6AM)
Our GWAS confirmed 11 genetic loci previously associated with leucocyte telomere length (LTL) and two novel loci in SCNN1D and PITPNM1. PheWAS of LTL identified 67 distinct clinical phenotypes associated with both short and long LTL. We demonstrated that several diseases associated with LTL were related to one another but were largely independent from LTL genetics. Age of death was correlated with LTL independent of age.
Evaluation of polygenic risk scores to differentiate between type 1 and type 2 diabetes.
Muhammad Shoaib et al. Genetic epidemiology 2023 2
(Posted: Mar 04, 2023 9AM)
We evaluated PRS models for T1D and T2D in European genetic ancestry participants from the UK Biobank (UKB) and then in the Michigan Genomics Initiative (MGI). Specifically, we investigated the utility of T1D and T2D PRS to discriminate between T1D, T2D, and controls in unrelated UKB individuals of European ancestry. We derived PRS models using external non-UKB GWAS. The T1D PRS model with the best discrimination between T1D cases and controls (area under the receiver operator curve [AUC]?=?0.805) also yielded the best discrimination of T1D from T2D cases in the UKB (AUC?=?0.792) and separation in MGI (AUC?=?0.686).
Identification of specific susceptibility loci for the early-onset colorectal cancer.
Haoxue Wang et al. Genome medicine 2023 3 (1) 13
(Posted: Mar 04, 2023 8AM)
We identified 49 independent susceptibility loci that were significantly associated with the susceptibility to EOCRC and the diagnosed age of CRC (both P < 5.0×10-4), replicating 3 previous CRC GWAS loci. There are 88 assigned susceptibility genes involved in chromatin assembly and DNA replication pathways, mainly associating with precancerous polyps. Additionally, we assessed the genetic effect of the identified variants by developing a PRS model.
15 years of GWAS discovery: Realizing the promise.
Abdellaoui Abdel et al. American journal of human genetics 2023 1
(Posted: Jan 20, 2023 6AM)
It has been 15 years since the advent of the genome-wide association study (GWAS) era. Here, we review how this experimental design has realized its promise by facilitating an impressive range of discoveries with remarkable impact on multiple fields, including population genetics, complex trait genetics, epidemiology, social science, and medicine.
Diet modulates genetic effects on longevity.
et al. Nature genetics 2023 1
(Posted: Jan 11, 2023 6AM)
Why some individuals live longer than others is of major interest across a range of scientific disciplines, from evolutionary biology to human health. Evolutionary theory tells us that lifespan-reducing alleles should be purged from the gene pool1, yet decades of genome-wide association studies (GWAS) and model organism studies have shown that such alleles persist. Here, we address one potential explanation for this conundrum, the idea that alleles that regulate lifespan do so only in certain contexts (known as ‘genotype-by-environment’ (GxE) effects).
DNA methylation provides molecular links underlying complex traits
Nature Genetics, January 2, 2023
(Posted: Jan 02, 2023 0PM)
We profiled human DNA methylation for 987 GTEx samples across nine tissues and characterized how genetic regulation of the methylome, compared with the transcriptome, contributes to GWAS phenotypes. This resource contributes to our understanding of molecular regulatory mechanisms in human tissues and their effects on complex traits.
Genetic futurism.
et al. Nature genetics 2022 12 (12) 1757
(Posted: Dec 16, 2022 8AM)
Large-scale genotyping and phenotyping efforts, including biobanks, have revolutionized our understanding of the genetic architecture of human traits and diseases. Years of ever-larger genome-wide association studies (GWAS) have produced a catalog of genetic variants that contribute to complex traits. A corollary of this research has been the development of personalized polygenic scores (PGS) or polygenic risk scores (PRS).
Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants
KG Aragam et al, Nature Genetics, December 6, 2022
(Posted: Dec 06, 2022 0PM)
The discovery of genetic loci associated with complex diseases has outpaced the elucidation of mechanisms of disease pathogenesis. Here we conducted a genome-wide association study (GWAS) for coronary artery disease (CAD) comprising 181,522 cases among 1,165,690 participants of predominantly European ancestry. We detected 241 associations, including 30 new loci. Cross-ancestry meta-analysis with a Japanese GWAS yielded 38 additional new loci.
Shared genetic influences between blood analyte levels and risk of severe COVID-19
HM Tanha et al, Cell Reports, November 6, 2022
(Posted: Nov 12, 2022 7AM)
Here we utilise GWAS summary statistics to study the shared genetic influences (pleiotropy) between severe COVID-19 and 344 blood analytes at the genome, gene and single nucleotide polymorphism levels. Our pleiotropy analyses genetically link blood levels of 71 analytes to severe COVID-19 in at least one of the three levels of investigation—suggesting shared biological mechanisms or causal relationships. Six analytes (alanine aminotransferase, alkaline phosphatase, apolipoprotein B, C-reactive protein, triglycerides, and urate) display evidence of pleiotropy with severe COVID-19 at all three levels.
Polygenic risk scores of endo-phenotypes identify the effect of genetic background in congenital heart disease.
Spendlove Sarah J et al. HGG advances 2022 5 (3) 100112
(Posted: Nov 07, 2022 8AM)
Here we used CHD-phenotype matched genome-wide association study (GWAS) summary statistics from the UK Biobank (UKBB) as our base study and whole-genome sequencing data from the CHD cohort (n1 = 711 trios, n2 = 362 European trios) of the Gabriella Miller Kids First dataset as our target study to develop PRSs for CHD. PRSs estimated using a GWAS for heart valve problems and heart murmur explain 2.5% of the variance in case-control status of CHD.
Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis.
Ishigaki Kazuyoshi et al. Nature genetics 2022 11
(Posted: Nov 06, 2022 8AM)
We present a large-scale genome-wide association study (GWAS) of RA, which includes 276,020 samples from five ancestral groups. We conducted a multi-ancestry meta-analysis and identified 124 loci (P?<?5?×?10-8), of which 34 are novel. Candidate genes at the novel loci suggest essential roles of the immune system (for example, TNIP2 and TNFRSF11A) and joint tissues (for example, WISP1) in RA etiology. PRS based on multi-ancestry GWAS outperformed PRS based on single-ancestry GWAS and had comparable performance between populations of European and East Asian ancestries.
Genetic Risk Factors for ME/CFS Identified using Combinatorial Analysis
S Das et al, MEDRXIV, September 9, 2022
(Posted: Sep 10, 2022 10AM)
We applied both GWAS and the PrecisionLife combinatorial analytics platform to analyze ME/CFS cohorts from UK Biobank, including the Pain Questionnaire cohort, in a case-control design with 1,000 cycles of fully random permutation. The results from this study were supported by a series of replication and cohort comparison experiments, including use of a disjoint Verbal Interview cohort also derived from UK Biobank, and results compared for reproducibility. Results: Combinatorial analysis revealed 199 SNPs mapping to 14 genes, that were significantly associated with 91% of the cases in the ME/CFS population.
Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk.
Yin Xianyong et al. American journal of human genetics 2022 9
(Posted: Sep 08, 2022 10AM)
Transcriptomics data have been integrated with genome-wide association studies (GWASs) to help understand disease/trait molecular mechanisms. The utility of metabolomics, integrated with transcriptomics and disease GWASs, to understand molecular mechanisms for metabolite levels or diseases has not been thoroughly evaluated.
Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention.
Wang Zhe et al. Nature genetics 2022 9
(Posted: Sep 08, 2022 6AM)
Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training.
GPNMB confers risk for Parkinson's disease through interaction with α-synuclein.
Diaz-Ortiz Maria E et al. Science (New York, N.Y.) 2022 8 (6608) eabk0637
(Posted: Aug 19, 2022 11AM)
Genome-wide association studies (GWAS) have uncovered nearly 100 loci that contribute to risk for Parkinson’s disease (PD), which affects an estimated 6 million people worldwide. However, target genes and biological mechanisms associated with these loci remain largely unexplored. Diaz-Ortiz et al. examined a PD GWAS risk locus on chromosome 7, linking it to the transmembrane protein Glycoprotein Nonmetastatic Melanoma Protein B (GPNMB). GPNMB was found to interact with alpha-synuclein (aSyn),
DOCK2 is involved in the host genetics and biology of severe COVID-19
H Namkoong et al, Nature, August 8, 2022
(Posted: Aug 08, 2022 7AM)
We conducted a genome-wide association study (GWAS) involving 2,393 Japanese COVID-19 cases collected in initial pandemic waves with 3,289 controls, which identified a variant on 5q35 (rs60200309-A) near DOCK2 associated with severe COVID-19 in younger (<65 ages) patients (nCase=440, odds ratio=2.01, P=1.2×10-8). This risk allele was prevalent in East Asians but rare in Europeans, showing a value of non-European GWAS. RNA-seq of 473 bulk peripheral blood identified decreasing effect of the risk allele on DOCK2 expression in younger patients. DOCK2 expression was suppressed in severe forms of COVID-19.
Shared mechanisms across the major psychiatric and neurodegenerative diseases
TS Wingo et al, Nat Comm, July 26, 2022
(Posted: Jul 26, 2022 7AM)
Using 25 GWAS results and LD score regression, we find eight significant genetic correlations between psychiatric and neurodegenerative diseases. We integrate the GWAS results with human brain transcriptomes (n?=?888) and proteomes (n?=?722) to identify cis- and trans- transcripts and proteins that are consistent with a pleiotropic or causal role in each disease, referred to as causal proteins for brevity. Within each disease group, we find many distinct and shared causal proteins. Remarkably, 30% (13 of 42) of the neurodegenerative disease causal proteins are shared with psychiatric disorders.
Development and validation of a trans-ancestry polygenic risk score for type 2 diabetes in diverse populations
T Ge et al, Genome Medicine, June 29, 2022
(Posted: Jun 29, 2022 6PM)
We integrated T2D GWAS in European, African, and East Asian populations to construct a trans-ancestry T2D PRS using a newly developed Bayesian polygenic modeling method, and assessed the prediction accuracy of the PRS in the multi-ethnic Electronic Medical Records and Genomics (eMERGE) study (11,945 cases; 57,694 controls), four Black cohorts (5137 cases; 9657 controls), and the Taiwan Biobank (4570 cases; 84,996 controls). We additionally evaluated a post hoc ancestry adjustment method that can express the polygenic risk on the same scale across ancestrally diverse individuals and facilitate the clinical implementation of the PRS in prospective cohorts.
Linking genetic variants to kidney disease via the epigenome
Nature Genetics, June 23, 2022
(Posted: Jun 25, 2022 11AM)
The largest GWAS for kidney function so far provided the starting point for integrated multi-stage annotation of genetic loci. Whole kidney and single-cell epigenomic information is crucial for translating GWAS information to the identification of causal genes and pathogenetic (and potentially targetable) cellular and molecular mechanisms of kidney disease.
Mendelian randomization analysis for attention deficit/hyperactivity disorder: studying a broad range of exposures and outcomes.
Soler Artigas María et al. International journal of epidemiology 2022 6
(Posted: Jun 18, 2022 10AM)
We used genome-wide association study (GWAS) summary statistics for ADHD (n?=?53?293) and 124 traits related to anthropometry, cognitive function and intelligence, early life exposures, education and employment, lifestyle and environment, longevity, neurological, and psychiatric and mental health or personality and psychosocial factors available in the MR-Base database (16?067 =n?=766?345). Our findings strengthen previous evidence of a causal effect of ADHD liability on smoking and major depression, and are consistent with a causal effect on odds of decreased average total household income [odds ratio (OR)?=?0.966, 95% credible interval (CrI)?=?(0.954, 0.979)] and increased lifetime number of sexual partners [OR?=?1.023, 95% CrI?=?(1.013, 1.033)].
Genome-wide polygenic score to predict chronic kidney disease across ancestries
A Khan et al, Nature Medicine, June 16, 2022
(Posted: Jun 16, 2022 0PM)
Chronic kidney disease (CKD) is a common complex condition associated with high morbidity and mortality. Polygenic prediction could enhance CKD screening and prevention; however, this approach has not been optimized for ancestrally diverse populations. By combining APOL1 risk genotypes with genome-wide association studies (GWAS) of kidney function, we designed, optimized and validated a genome-wide polygenic score (GPS) for CKD. The new GPS was tested in 15 independent cohorts, including 3 cohorts of European ancestry (n?=?97,050), 6 cohorts of African ancestry (n?=?14,544), 4 cohorts of Asian ancestry (n?=?8,625) and 2 admixed Latinx cohorts (n?=?3,625).
The missing diversity in human epigenomic studies
CE Breeze, Nature Genetics, June 9, 2022
(Posted: Jun 10, 2022 7AM)
Recent work has highlighted a lack of diversity in genomic studies. However, less attention has been given to epigenomics. Here, we show that epigenomic studies are lacking in diversity and propose several solutions to address this problem. Current efforts to increase representation in genomic research in diverse populations should be paired with similar efforts in epigenomics, which have, thus far, received less attention and scientific scrutiny. Adding ancestry information, which could be inferred from sequencing or genotype array data, to existing epigenomic data could be beneficial in helping researchers understand the potential limitations for annotating and interpreting GWAS loci from different populations.
Extending precision medicine tools to populations at high risk of type 2 diabetes.
Misra Shivani et al. PLoS medicine 2022 5 (5) e1003989
(Posted: May 28, 2022 11AM)
The generation of ethnicity-specific T2D PS for every subethnic group remains aspirational, as the large sample sizes needed to do this robustly are prohibitive (the genetic ancestry of the Indian subcontinent, for example, is more diverse than the whole of Europe. Thus, strategies to utilise existing scores derived from other populations, or leveraging multi-ancestry GWAS, have predominated. Attempts to apply a PS derived in a population of one ancestry to another ethnic group have shown variable performance.
Host genetic basis of COVID-19: from methodologies to genes
K Zguro et al, EJHG, May 27, 2022
(Posted: May 27, 2022 5AM)
This review delineates GWAS and Burden test as traditional methodologies employed so far for the discovery of the human genetic basis of COVID-19, with particular attention to recently emerged predictive models such as the post-Mendelian model. A summary table with the main genome-wide significant genomic loci is provided. Besides, various common and rare variants identified in genes like TLR7, CFTR, ACE2, TMPRSS2, TLR3, and SELP are further described in detail to illustrate their association with disease severity.
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation.
Mahajan Anubha et al. Nature genetics 2022 5 (5) 560-572
(Posted: May 18, 2022 11AM)
We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability
Improving polygenic prediction in ancestrally diverse populations
Y Ruan et al, Nature Genetics, May 5, 2022
(Posted: May 05, 2022 2PM)
Polygenic risk scores (PRS) have attenuated cross-population predictive performance. As existing genome-wide association studies (GWAS) have been conducted predominantly in individuals of European descent, the limited transferability of PRS reduces their clinical value in non-European populations, and may exacerbate healthcare disparities. Recent efforts to level ancestry imbalance in genomic research have expanded the scale of non-European GWAS, although most remain underpowered. Here, we present a new PRS construction method, PRS-CSx, which improves cross-population polygenic prediction by integrating GWAS summary statistics from multiple populations.
Host Genomics and COVID-19: Two Years Later
E Drzymalla et al, CDC Blog Post, May 3, 2022
(Posted: May 03, 2022 2PM)
As we head to the next phase of identifying actionable insights, it is important to acknowledge the inevitable time lag between genetic discovery and clinical implementation. It may be fruitful to recall lessons learned from past studies and the exemplars of GWAS successes. Currently, GWAS results are valuable for research purposes, but are unlikely to have a clinical value in the short term, and have a limited impact on the management of the COVID-19 pandemic thus far. The ultimate hope is to use host genetic findings to guide the development of future therapies, and enable effective prevention of severe COVID-19.
Using Pharmacogenomics to Better Understand the Role of Selected Medications and Birth Defect Risk
M Jenkins et al, CDC Blog Post, April 12, 2022
(Posted: Apr 12, 2022 2PM)
The NBDPS allows researchers to investigate gene-medication associations because it collected information on the timing, duration, and frequency of medication use, and has a diverse racial and ethnic study population, representative of the population of the United States. Analyzing GWAS data from this unique dataset could lead to improvements in health equity for medication safety for pregnant women. These analyses are expected to advance precision medicine by identifying individuals with higher genetic risk for birth defects via polygenic risk scores, as well as identifying medication targets.
Polygenic scores in biomedical research
IJ Kullo et al, Nature Reviews Genetics, March 30, 2022
(Posted: Mar 30, 2022 10AM)
Genome-wide association studies (GWAS) have implicated thousands of single-nucleotide polymorphisms (SNPs) in common complex diseases or traits. By calculating a weighted sum of the number of trait-associated alleles harboured by an individual, a polygenic score (PGS), also called a polygenic risk score (PRS), can be constructed that reflects an individual’s estimated genetic predisposition for a given phenotype. Here, 6 experts give their opinions on the utility of these probabilistic tools, their strengths and limitations, and the remaining barriers that need to be overcome for their equitable use.
Enrichment analyses identify shared associations for 25 quantitative traits in over 600,000 individuals from seven diverse ancestries
SP Smith et al, AJHG, March 28, 2022
(Posted: Mar 28, 2022 2PM)
We illustrate examples of the robust associations generated by enrichment analyses while studying 25 continuous traits assayed in 566,786 individuals from seven diverse self-identified human ancestries in the UK Biobank and the Biobank Japan as well as 44,348 admixed individuals from the PAGE consortium including cohorts of African American, Hispanic and Latin American, Native Hawaiian, and American Indian/Alaska Native individuals. We identify 1,000 gene-level associations that are genome-wide significant in at least two ancestry cohorts across these 25 traits as well as highly conserved pathway associations with triglyceride levels in European, East Asian, and Native Hawaiian cohorts.
GWAS and meta-analysis identifies multiple new genetic mechanisms underlying severe Covid-19.
EP Castineira et al, MEDRXIV, March 7, 2022
(Posted: Mar 08, 2022 7AM)
In this new data release from the GenOMICC (Genetics Of Mortality in Critical Care) study we include new microarray genotyping data from additional critically-ill cases in the UK and Brazil, together with cohorts of severe Covid-19 from the ISARIC4C and SCOURGE studies, and meta-analysis with previously-reported data. We find an additional \numconvincingnew new genetic associations. Many are in potentially druggable targets, in inflammatory signalling (JAK1, PDE4A), monocyte-macrophage differentiation (CSF2), immunometabolism (SLC2A5, AK5), and host factors required for viral entry and replication (TMPRSS2, RAB2A).
Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility
J Barc et al, Nature Genetics, February 24, 2022
(Posted: Feb 25, 2022 9AM)
Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population.
GWAS of longitudinal trajectories at biobank scale.
Ko Seyoon et al. American journal of human genetics 2022 2
(Posted: Feb 24, 2022 9AM)
Compared to traditional cross-sectional studies, trajectory analysis utilizes more data points and captures a complete picture of the impact of time-varying factors, including medication history and lifestyle. Currently, there are no efficient tools for genome-wide association studies (GWASs) of biomarker trajectories at the biobank scale, even for just mean effects. We propose TrajGWAS, a linear mixed effect model-based method for testing genetic effects that shift the mean or alter the WS variability of a biomarker trajectory. It is scalable to biobank data with 100,000 to 1,000,000 individuals and many longitudinal measurements and robust to distributional assumptions.
A year of Covid-19 GWAS results from the GRASP portal reveals potential genetic risk factors
F Thibord et al, AJHG, February 22, 2022
(Posted: Feb 23, 2022 9AM)
In coherence with previous studies, we observed 2 independent signals at the chr3p21.31 locus (rs73062389-A, OR=1.21, P=4.26×10-15 and rs71325088-C, OR=1.62, P=2.25×10-9) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A, OR=1.10, P=3.30×10-12), suggesting an increased risk of infection in non-O blood groups carriers. Additional signals at the APOE (associated with severity and death) LRMDA (susceptibility in non-European) and chr2q32.3 (susceptibility in women) loci were also identified but did not replicate in independent datasets.
Accounting for age of onset and family history improves power in genome-wide association studies.
Pedersen Emil M et al. American journal of human genetics 2022 2
(Posted: Feb 10, 2022 0PM)
Genome-wide association studies (GWASs) have revolutionized human genetics, allowing researchers to identify thousands of disease-related genes and possible drug targets. However, case-control status does not account for the fact that not all controls may have lived through their period of risk for the disorder of interest. This can be quantified by examining the age-of-onset distribution and the age of the controls or the age of onset for cases. The age-of-onset distribution may also depend on information such as sex and birth year. In addition, family history is not routinely included in the assessment of control status. Using simulation, we show that, when family history and the age-of-onset distribution are available, the proposed approach yields statistically significant power gains over LT-FH and large power gains over genome-wide association study by proxy (GWAX).
Microbial GWAS studies revealing combinations of Omicron RBD mutations existed and may contribute to antibody evasion and ACE2 binding
X Ou et al, MEDRXIV, January 21, 2022
(Posted: Jan 22, 2022 1PM)
Polygenic Prediction of Type 2 Diabetes in Africa.
Chikowore Tinashe et al. Diabetes care 2022 1
(Posted: Jan 18, 2022 7AM)
Polygenic prediction of type 2 diabetes (T2D) in continental Africans is adversely affected by the limited number of genome-wide association studies (GWAS) of T2D from Africa and the poor transferability of European-derived polygenic risk scores (PRSs) in diverse ethnicities. We set out to evaluate if African American–, European-, or multiethnic-derived PRSs would improve polygenic prediction in continental Africans.
The power of genetic diversity in genome-wide association studies of lipids
SE Graham et al, Nature, December 9, 2021
(Posted: Dec 12, 2021 9AM)
We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately?295,000 individuals from 7?ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine.
Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology
W van Rheenen et al, Nature Genetics, December 6, 2021
(Posted: Dec 07, 2021 7AM)
We conducted a cross-ancestry genome-wide association study (GWAS) including 29,612 patients with ALS and 122,656 controls, which identified 15 risk loci. When combined with 8,953 individuals with whole-genome sequencing (6,538 patients, 2,415 controls) and a large cortex-derived expression quantitative trait locus (eQTL) dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, short tandem repeats or regulatory effects. ALS-associated risk loci were shared with multiple traits within the neurodegenerative spectrum but with distinct enrichment patterns across brain regions and cell types. Of the environmental and lifestyle risk factors obtained from the literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels.
On powerful GWAS in admixed populations
K Hou et al, Nature Genetics, November 2021
(Posted: Nov 27, 2021 9AM)
Mapping the human genetic architecture of COVID-19: an update
The COVID-19 Host Genetics Initiative, MEDRXIV, November 11, 2021
(Posted: Nov 12, 2021 7AM)
The Coronavirus Disease 2019 (COVID-19) pandemic continues to pose a major public health threat especially in countries with low vaccination rates. To better understand the biological underpinnings of SARS-CoV-2 infection and COVID-19 severity we formed the COVID19 Host Genetics Initiative. Here we present GWAS meta-analysis of up to 125,584 cases and over 2.5 million controls across 60 studies from 25 countries, adding 10 new genome-wide significant loci to the 13 we previously identified1. Genes in novel loci include SFTPD, MUC5B and ACE2, reveal compelling insights regarding disease susceptibility and severity.
SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a wide variety of tiss
M d'Antonio et al, Cell Reports, November 2, 2021
(Posted: Nov 03, 2021 4PM)
Highlights: Identification of 23 genomic loci with suggestive associations for COVID-19 disease. Colocalized GWAS & eQTL signals associate with expression of 20 genes in 62 tissues. 45% of GWAS signals do not colocalize with eQTLs in blood or lung. Genetic fine mapping identifies putative causal variants at COVID-19 GWAS loci.
Exome sequencing and analysis of 454,787 UK Biobank participants
JD Backman et al, Nature, October 19, 2021
(Posted: Oct 19, 2021 6AM)
A major goal in human genetics is to use natural variation to understand the phenotypic consequences of altering each protein-coding gene in the genome. Here we used exome sequencing1 to explore protein altering variants and their consequences in 454,787 UK Biobank study participants. We identified 12 million coding variants, including ~1 million loss-of-function and ~1.8 million deleterious missense variants. When these were tested for association with 3,994 health-related traits, we found 564 genes with trait associations at P=2.18x10-11. Rare variant associations were enriched in GWAS loci, but most (91%) were independent of common variant signals.
A cross-population atlas of genetic associations for 220 human phenotypes
S Sakaue et al, Nature Genetics, September 30, 2021
(Posted: Oct 01, 2021 6AM)
To expand an atlas of genetic associations in non-European populations, we conducted 220 deep-phenotype genome-wide association studies (diseases, biomarkers and medication usage) in BioBank Japan (n?=?179,000), by incorporating past medical history and text-mining of electronic medical records. Meta-analyses with the UK Biobank and FinnGen (ntotal?=?628,000) identified ~5,000 new loci, which improved the resolution of the genomic map of human traits. This atlas elucidated the landscape of pleiotropy as represented by the major histocompatibility complex locus, where we conducted HLA fine-mapping.
The genetics of obesity: from discovery to biology
RJF Loos et al, Nat Rev Genetics, September 23, 2021
(Posted: Sep 24, 2021 6AM)
Genome-wide association studies (GWAS) with increasing sample sizes and advances in sequencing technology are the main drivers behind a recent flurry of new discoveries. However, it is the post-GWAS, cross-disciplinary collaborations, which combine new omics technologies and analytical approaches, that have started to facilitate translation of genetic loci into meaningful biology and new avenues for treatment.
A year of Covid-19 GWAS results from the GRASP portal reveals potential SARS-CoV-2 modifiers
F Thibord et al, MEDRXIV, September 5, 2021
(Posted: Sep 06, 2021 6AM)
Between May 2020 and June 2021, we used Covid-19 data released periodically by UK Biobank and performed 65 Genome-Wide Association Studies (GWAS) in up to 18 releases of Covid-19 susceptibility (N=18,481 cases in June 2021), hospitalization (N=3,260), severe outcomes (N=1,244) and death (N=1,104), stratified by sex and ancestry. In coherence with previous studies, we observed 2 independent signals at the chr3p21.31 locus (rs73062389-A, OR=1.21, P=4.26E-15 and rs71325088-C, OR=1.62, P=2.25E-9) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A, OR=1.10, P=3.30E-12).
Genome-wide association studies
E Uffelmann et al, Nat Rev Dis Primers, August 2021
(Posted: Sep 01, 2021 7AM)
Genome-wide association studies (GWAS) test hundreds of thousands of genetic variants across many genomes to find those statistically associated with a specific trait or disease. This methodology has generated a myriad of robust associations for a range of traits and diseases, and the number of associated variants is expected to grow steadily as GWAS sample sizes increase. GWAS results have a range of applications, such as gaining insight into a phenotype’s underlying biology, estimating its heritability, calculating genetic correlations, making clinical risk predictions, informing drug development programs and inferring potential causal relationships between risk factors and health outcomes.
Vexed causal inferences in nutritional epidemiology-call for genetic help.
Ohukainen Pauli et al. International journal of epidemiology 2021 8
(Posted: Aug 23, 2021 7AM)
Mendelian randomization is a form of instrumental variable analysis used to assess causality of exposures using genetic data and it has become increasingly popular in epidemiology over the past decade. A clear distinction should be made between Mendelian randomization and a GWAS, the former being based on the latter. This is also reflected in the interpretation of results: a GWAS provides genetic associations in a general sense but the Mendelian randomization framework assesses potential causal effects.
Ten simple rules for conducting a mendelian randomization study.
Gagliano Taliun Sarah A et al. PLoS computational biology 2021 8 (8) e1009238
(Posted: Aug 19, 2021 8AM)
Given the growing number of MR studies in the literature and the increasing amount of publicly available genome-wide association study (GWAS) datasets and variant–trait association summary statistics, which make such studies feasible, we describe 10 simple rules for conducting an MR study. Our aim is not to provide a comprehensive and detailed overview of MR (which can be found elsewhere, but rather to present a starting place for researchers to prepare to conduct and to begin to critically evaluate existing MR studies.
Genetic variations could one day help predict timing of menopause
H Ledford, Nature News, August 4, 2021
(Posted: Aug 05, 2021 11AM)
A study of more than 200,000 women has revealed hundreds of genetic variants involved in determining the age at which they experienced menopause. Many of the 290 variants govern how the body responds to immature eggs with damaged DNA1, highlighting the importance of these processes and suggesting that they could one day be harnessed to extend people's natural reproductive lifespans, or improve the success rate of in vitro fertilization techniques.
Finding a Place for Candidate Gene Studies in a Genome-Wide Association Study World
DK Menon et al, JAMA Network Open, July 26, 2021
(Posted: Jul 27, 2021 7AM)
GWAS are unbiased and data-driven, can address millions of common genetic variants, and have well-accepted thresholds for multiple comparison. While GWAS is generally applied to case-control samples, it can also be applied to quantitative traits in affected individuals. Given this background, it is legitimate to ask whether candidate gene studies, which restrict their assessment to individual genes or genome regions based on an a priori biological hypothesis, still have a role in understanding disease biology and supporting better practice.
Advancing the use of genome-wide association studies for drug repurposing
WR Reay et al, Nat Rev Genetics, July 2021
(Posted: Jul 25, 2021 6AM)
We explore approaches that leverage common variant genetics to identify opportunities for repurposing existing drugs, also known as drug repositioning. These approaches include the identification of compounds by linking individual loci to genes and pathways that can be pharmacologically modulated, transcriptome-wide association studies, gene-set association, causal inference by Mendelian randomization, and polygenic scoring.
New susceptibility loci for severe COVID-19 by detailed GWAS analysis in European populations
F Degenhardt et al, MEDRXIV, July 23, 2021
(Posted: Jul 24, 2021 8AM)
We describe an extended GWAS meta-analysis of 3,260 COVID-19 patients with respiratory failure and 12,483 population controls from Italy, Spain, Norway and Germany, as well as hypothesis-driven targeted analysis of the human leukocyte antigen (HLA) region and chromosome Y haplotypes. We include detailed stratified analyses based on age, sex and disease severity. In addition to already established risk loci, our data identify and replicate two genome-wide significant loci at 17q21.31 and 19q13.33 associated with severe COVID-19 with respiratory failure.
Contextualizing genetic risk score for disease screening and rare variant discovery
D Zhou et al, Nature Comms, July 20, 2021
(Posted: Jul 21, 2021 7AM)
Studies of the genetic basis of complex traits have demonstrated a substantial role for common, small-effect variant polygenic burden (PB) as well as large-effect variants (LEV, primarily rare). We identify sufficient conditions in which GWAS-derived PB may be used for well-powered rare pathogenic variant discovery or as a sample prioritization tool for whole-genome or exome sequencing.
Finding genes that control body weight
GSH Yeo et al, Science, July 2, 2021
(Posted: Jul 02, 2021 7AM)
The principles of discovery go beyond that of body weight control and obesity. The exome sequencing approach at scale increases our ability to reach deep into the rare allele frequency spectrum for functionally compromised alleles. It bypasses the twin headaches of GWAS: the identification of the causative gene and the determination of direction of causality.
A year of COVID-19 GWAS results from the GRASP portal reveals potential SARS-CoV-2 modifiers
F Thibord et al, MEDRXIV, June 11, 2021
(Posted: Jun 11, 2021 7AM)
Between May 2020 and February 2021, we used Covid-19 data from UK Biobank and performed over 400 Genome-Wide Association Studies (GWAS) of Covid-19 susceptibility (N=15,738 cases), hospitalization (N=1,916), severe outcomes (N=935) and death (N=828), We observed 2 independent signals at the chr3p21.31 locus (rs73062389-A, OR=1.22, P=7.64E-14 and rs13092887-A, OR=1.73, P=2.38E-8, in Europeans) modulating susceptibility and severity, respectively, and a signal influencing susceptibility at the ABO locus (rs9411378-A, OR=1.10, P =7.36E-10, in Europeans).
Expanding Discovery in Cardiovascular Genome-Wide Association Studies
P Natarajan et al, JAMA Cardiology, June 9, 2021
(Posted: Jun 10, 2021 7AM)
Genome-wide association studies of individuals of African ancestry typically living in the US are uncommon, yet they have yielded high-impact observations, including the discovery that PCSK9 loss-of-function mutations protect against coronary artery disease. Genome-wide association studies of individuals living in Africa are even rarer, representing approximately 0.4% of GWAS participants.
The UGT2A1/UGT2A2 locus is associated with COVID-19-related anosmia
JF Shelton et al, MEDRXIV, May 31, 2021
(Posted: Jun 01, 2021 10AM)
We ran a trans-ethnic genome-wide association study (GWAS) comparing loss of smell or taste (n=47,298) with no loss of smell or taste (n=22,543) among those with a positive SARS-CoV-2 test result. We identified an association (rs7688383) in the vicinity of the UGT2A1 and UGT2A2 genes (OR=1.115, p-value=4x10-15), which have been linked to olfactory function. These results may shed light on the biological mechanisms underlying COVID-19 related anosmia.
GWAS Diversity Monitor
NHGRI-EMBL GWAS Catalog, April 2021
(Posted: Apr 27, 2021 8AM)
This interactive dashboard monitors the diversity of participants across all published Genome Wide Association Studies (GWAS), the primary technique used for genetic discovery. The objective of a GWAS is to identify statistical associations between a set of genetic variants across different individuals (Single Nucleotide Polymorphisms, or 'SNPs') with specific traits of interest.
Integrative approach identifies SLC6A20 and CXCR6 as putative causal genes for the COVID-19 GWAS signal in the 3p21.31 locus
S Kazela et al, MEDRXIV, April 13, 2021
(Posted: Apr 13, 2021 0PM)
Genome-wide association study in 8,956 German individuals identifies influence of ABO histo-blood groups on gut microbiome
MC Ruhleman et al, Nature Genetics, January 18, 2021
(Posted: Jan 19, 2021 8AM)
In a GWAS of 8,956 German individuals, we identified 38 genetic loci to be associated with single bacteria and overall microbiome composition. Further analyses confirm the identified associations of ABO histo-blood groups and FUT2 secretor status with Bacteroides and Faecalibacterium spp. Mendelian randomization analysis suggests causative and protective effects of gut microbes.
Functional studies of GWAS variants are gaining momentum
F Lichou, Nature Communications, December 2020
(Posted: Dec 16, 2020 8AM)
Rapidly advancing genomic technologies and cross-disciplinary partnerships are accelerating the biological and clinical interpretation of genome-wide association studies, with some therapies developed based on these findings already being tested in clinical trials. The next decade promises further progress in understanding the function of genetic variants.
Genetic mechanisms of critical illness in Covid-19
E Pairo-Castineira et al, Nature, December 11, 2020
(Posted: Dec 11, 2020 3PM)
This is a genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units. We identify novel genome-wide significant associations, on chr12q24.13 in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 in the interferon receptor gene IFNAR2.
15 Years of Genome-wide Association Studies: What’s the Public Health Impact?
MJ Khoury et al, December 8, 2020
(Posted: Dec 09, 2020 9AM)
Most research translating GWAS findings has taken one of two paths: The first pursues biological insights that could lead to new therapies. The second path makes use of population-level data and statistical methods to develop indicators of disease risk. The two leading examples of this approach are polygenic risk scores and Mendelian randomization.
Mining a GWAS of Severe Covid-19
DH Katz et al, NEJM, November 24, 2020
(Posted: Nov 25, 2020 10AM)
The COVID-19 genetic risk variant rs657152-A at the ABO locus is strongly associated with increased levels of the CD209 antigen. This dendritic cell-surface protein has been found to facilitate infection by SARS-CoV-2 and other viruses.
15 years of genome-wide association studies and no signs of slowing down
RJF Loos, Nature Comms, November, 2020
(Posted: Nov 25, 2020 9AM)
Over the past 15 years, genome-wide association studies (GWASs) have generated a wealth of new information. Larger samples sizes, refined phenotypes and higher-resolution genome-screens will continue to drive gene discovery in years ahead. Meanwhile, GWAS loci are increasingly translated into new biology and opportunities for clinical care.
The landscape of host genetic factors involved in immune response to common viral infections
L Kachuri et al, MEDRXIV, September 8, 2020
(Posted: Sep 09, 2020 9AM)
We conducted a genome-wide and transcriptome-wide association analyses to identify genetic loci associated with immunoglobulin G antibody response to 28 antigens for 16 viruses using serological data from 7924 European ancestry participants in the UK Biobank. The study confirms the importance of the HLA region in host response to viral infection and elucidates novel genetic determinants beyond HLA.
Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.
Thomas Minta et al. American journal of human genetics 2020 Jul
(Posted: Aug 09, 2020 0PM)
We are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. 90% of these individuals have no family history and would have been considered average risk under current screening guidelines.
The association of alcohol polygenic risk scores with mental health outcomes: A multi-generational analysis in the Avon Longitudinal Study of Parents and Children
KE Easey et al, MEDRXIV, July 7, 2020
(Posted: Jul 08, 2020 6AM)
An alcohol PRS derived from GWAS of alcohol use in the general population was shown to be associated with frequency and amount of alcohol consumed during pregnancy, and maternal depression at 32 weeks gestation.
Identification of type 2 diabetes loci in 433,540 East Asian individuals
CN Spracklen et al, Nature, May 6, 2020
(Posted: May 08, 2020 9AM)
We carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D
From GWAS to GEMMs: Sestrin1 and cholesterol biosynthesis
EJ Gallagher, Sci Trans Med, April 15, 2020
(Posted: Apr 17, 2020 9AM)
Assessing Digital Phenotyping to Enhance Genetic Studies of Human Diseases.
DeBoever Christopher et al. American journal of human genetics 2020 Apr
(Posted: Apr 11, 2020 8AM)
We evaluate whether GWAS performed using cases in the UK Biobank ascertained from hospital records, questionnaire responses, and family history implicate similar disease genetics. We show that digital phenotyping and unstructured phenotype data can be combined with structured data to identify cases and improve ability to identify genetic associations.
Genome-Wide Association Studies
X Guo et al, JAMA, November 5, 2019
(Posted: Nov 07, 2019 8AM)
GWAS take advantage of variation in the millions of known SNPs, occurring in known locations across the entire genome, to determine whether one genetic variant (ie, allele) at the location of each SNP occurs more often than expected in individuals with a particular disease than in those without the disease.
Genome-wide association studies of structural birth defects: A review and commentary.
Lupo Philip J et al. Birth defects research 2019 Oct
(Posted: Oct 31, 2019 0PM)
While there is strong evidence that genetic risk factors play an important role in the etiologies of structural birth defects, compared to other diseases, there have been relatively few GWAS of these conditions. We reviewed the current landscape of GWAS conducted for birth defects, noting novel insights, and future directions.
GWAS Identifies 44 Independent Associated Genomic Loci for Self-Reported Adult Hearing Difficulty in UK Biobank
HRR Wells et al, AJHG, September 26, 2019
(Posted: Sep 28, 2019 8AM)
Genome-wide association studies (GWASs) for two self-reported hearing phenotypes, using more than 250,000 UK Biobank (UKBB) volunteers aged between 40 and 69 years. Forty-four independent genome-wide significant loci were identified, considerably increasing the number of established trait loci.
GWAS including 82,707 subjects identifies functional coding variant in OPRM1 gene associated with opioid use disorder
H Zhou et al, MedRXIV, September 18, 2019
(Posted: Sep 19, 2019 9AM)
Cross-disorder GWAS meta-analysis for Attention Deficit/Hyperactivity Disorder, Autism Spectrum Disorder, Obsessive Compulsive Disorder, and Tourette Syndrome
Z Yang et al, BioRXIV, September 16, 2019
(Posted: Sep 17, 2019 7AM)
Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes
H Wang et al, Nature Comm, August 13, 2019
(Posted: Aug 14, 2019 8AM)
Assessment of Polygenic Architecture and Risk Prediction based on Common Variants Across Fourteen Cancers
Y Zhan et al, BioRXIV preprint, August 9, 2019
(Posted: Aug 10, 2019 9AM)
The study analyzed summary-level data from genome-wide association studies (GWAS) of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) contributing to risk, as well as the distribution of their associated effect sizes. All cancers evaluated showed polygenicity.
Convergence of recent GWAS data for suicidality with previous blood biomarkers: independent reproducibility using independent methodologies in independent cohorts.
Niculescu A B et al. Molecular psychiatry 2019 Aug
(Posted: Aug 08, 2019 8AM)
Biases in GWAS the dog that did not bark
CM Schooling, BIoRXIV preprints, July 20, 2019
(Posted: Jul 22, 2019 8AM)
Identification of type 2 diabetes loci in 433,540 East Asian individuals
CN Spracklen et al, BioRXIV, June 28, 2019
(Posted: Jun 29, 2019 5PM)
To examine Type 2 diabtes risk in East Asian individuals, the authors meta-analyzed GWAS data in 77,418 cases and 356,122 controls. The study identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, the study identified 56 loci newly implicated in T2D predisposition
Benefits and limitations of genome-wide association studies
V Tam et al, Nature Rev Genetics, May 2019
(Posted: May 08, 2019 11AM)
GWAS of smoking behaviour in 165,436 Japanese people reveals seven new loci and shared genetic architecture
N Matoba et al, Nature Human Behavior, March 25, 2019
(Posted: Mar 26, 2019 9AM)
A scientometric review of genome-wide association studies
MC Mills, Nature Communications Biology, January 2019
(Posted: Feb 10, 2019 1PM)
Life after GWAS where to next, for psychiatric genetics?
K Mitchell, Wiring the Brain, November 5, 2018
(Posted: Nov 06, 2018 9AM)
An atlas of genetic associations in UK Biobank
O Canela-Xandri et al, Nature Genetics, October 22, 2018
(Posted: Oct 22, 2018 2PM)
GWAS to the people
Nature Medicine editorial, October 8, 2018
(Posted: Oct 09, 2018 9AM)
Why Do Polygenic Risk Scores Get So Much Hype? GWAS for Common Disease Variants Gains Prominence
J Lemieux, GEN< August 22, 2018
(Posted: Aug 23, 2018 10AM)
GWAS catalog
CDC Public Health Genomics Knowledge Base
(Posted: Jul 13, 2018 9AM)
10th Anniversary of the NHGRI-EBI GWAS Catalog
GWAS catalog, 2018
(Posted: Jul 13, 2018 8AM)
