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Coronary Artery Disease Risk Loci, Candidate Genes Identified in GWAS Meta-Analysis

For a paper in Nature Genetics, a team from Massachusetts General Hospital, the Broad Institute, the University of Cambridge, and elsewhere present findings from a large coronary artery disease (CAD) genome-wide association study. With genotyping profiles for more than 210,842 cases and almost 1.2 million controls, the team initially identified 241 CAD associations, uncovering another 38 risk loci through a cross-ancestry meta-analysis. In their follow-up fine mapping and functional analyses, including CRISPR-Cas9-based gene editing experiments, the authors focused in on 220 candidate causal genes, including a Rho-GTPase-related, myosin protein-coding gene called MYO9B. "[W]e experimentally validated the effect of an enhancer in MYO9B, which appears to mediate CAD risk by regulating vascular cell motility," the authors write, noting that "experimental evidence is ultimately required to confirm causal mechanisms at all unresolved CAD risk loci."

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.