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Last Posted: Aug 17, 2023
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We need a genomics-savvy healthcare workforce
Nature Medicine, August 16, 2023

The increasingly central role of genomics in healthcare means that not only are more genetic counselors needed, but also multidisciplinary teams are essential for utilizing genomic technologies in the clinical setting. Genomic tests (such as those based on whole-exome or whole-genome sequencing) generate an enormous amount of highly complex data, which requires professionals with specialized bioinformatic skills and the know-how to operate within clinically accredited frameworks. In addition, although genomics is currently the most common ‘-omic’ used in the clinic, transcriptomics and proteomics are also being incorporated into algorithms to inform clinical practice.

Converging evidence from exome sequencing and common variants implicates target genes for osteoporosis
S Zhou et al, Nature Genetics, August 9, 2023

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.

Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer's disease.
Erik C B Johnson et al. Nat Med 2023 8

Here we show that proteomic measurements in autosomal dominant AD cerebrospinal fluid (CSF) linked to brain protein coexpression can be used to characterize the evolution of AD pathology over a timescale spanning six decades. SMOC1 and SPON1 proteins associated with Aß plaques were elevated in AD CSF nearly 30 years before the onset of symptoms, followed by changes in synaptic proteins, metabolic proteins, axonal proteins, inflammatory proteins and finally decreases in neurosecretory proteins. The proteome discriminated mutation carriers from noncarriers before symptom onset as well or better than Aß and tau measures.

Proteomics analysis of plasma from middle-aged adults identifies protein markers of dementia risk in later life.
Keenan A Walker et al. Sci Transl Med 2023 7 (705) eadf5681

Here, we used a large-scale proteomics platform to examine the association of 4877 plasma proteins with 25-year dementia risk in 10,981 middle-aged adults. We found 32 dementia-associated plasma proteins that were involved in proteostasis, immunity, synaptic function, and extracellular matrix organization. We then replicated the association between 15 of these proteins and clinically relevant neurocognitive outcomes in two independent cohorts. We demonstrated that 12 of these 32 dementia-associated proteins were associated with cerebrospinal fluid (CSF) biomarkers of AD, neurodegeneration, or neuroinflammation.

Disclaimer: Articles listed in the Public Health Genomics and Precision Health Knowledge Base are selected by the CDC Office of Public Health Genomics to provide current awareness of the literature and news. Inclusion in the update does not necessarily represent the views of the Centers for Disease Control and Prevention nor does it imply endorsement of the article's methods or findings. CDC and DHHS assume no responsibility for the factual accuracy of the items presented. The selection, omission, or content of items does not imply any endorsement or other position taken by CDC or DHHS. Opinion, findings and conclusions expressed by the original authors of items included in the update, or persons quoted therein, are strictly their own and are in no way meant to represent the opinion or views of CDC or DHHS. References to publications, news sources, and non-CDC Websites are provided solely for informational purposes and do not imply endorsement by CDC or DHHS.