In Nature this week, investigators from the US and Mexico present a study demonstrating how genome-wide association studies can benefit from the use of diverse populations. To date, most drug discovery is conducted using genetic data from individuals of European descent despite the differences in genetic architecture and/or causal variants between populations, they write. To show the value in diverse, multi-ethnic participants in large-scale genomic studies, the researchers conducted a GWAS of 26 clinical and behavioral phenotypes in 49,839 non-European individuals. Using a framework for analyzing diverse populations, they identify 27 novel loci and 38 secondary signals at known loci, as well as replicate 1,444 GWAS catalog associations across these traits. "Our data show evidence of effect-size heterogeneity across ancestries for published GWAS associations, substantial benefits for fine-mapping using diverse cohorts, and [yield] insights into clinical implications," they write.
In Nature Genetics, a team of Asian and US scientists report how genome sequencing reveal subtypes of Epstein-Barr virus (EBV) that are associated with a high risk of nasopharyngeal carcinoma (NPC), one of the many different cancers linked to infection with the virus. The researchers performed large-scale whole-genome sequencing of EBV isolates from Chinese individuals — including 215 isolates patients with EBV-associated cancers and 54 isolates from healthy controls — to find two non-synonymous virus variants in a gene called BALF2 that are strongly associated with NPC risk. A follow-on genome-wide association study helped validate the findings. Overall, the study suggests that the cumulative effects of these variants contribute to 83 percent of the overall risk of NPC in southern China, and points to a uniquely Asian origin of the variants, the authors write.
And in Nature Neuroscience, a research group led by scientists from Aarhus University publishes a genome-wide association study implicating the gene CHRNA2 — a known nicotine receptor — with cannabis use disorder (CUD). They analyzed the genomes of 2,387 individuals with CUD and nearly 49,000 healthy controls — all from a Danish nationwide cohort — and linked a genetic variant that controls the expression of CHRNA2 with the disorder. An additional analysis in 5,501 cases and roughly 301,000 controls replicated the finding. "The results provide biological insights and inform on the genetic architecture of CUD," and could potentially lead to new treatments for CUD, the researchers conclude.