Among US adults, DSM-5 MDD is highly prevalent, comorbid, and disabling. While most cases received some treatment, a substantial minority did not. Much remains to be learned about the DSM-5 MDD specifiers in the general population.
Liability to alcohol dependence (AD) is heritable, but little is known
about its complex polygenic architecture or its genetic relationship with other
disorders. To discover loci associated with AD and characterize the relationship
between AD and other psychiatric and behavioral outcomes, we carried out the
largest GWAS to date of DSM-IV diagnosed AD. Genome-wide data on 14,904
individuals with AD and 37,944 controls from 28 case/control and family-based
studies were meta-analyzed, stratified by genetic ancestry (European, N =
46,568; African; N = 6,280). Independent, genome-wide significant effects of
different ADH1B variants were identified in European
(rs1229984; p = 9.8E-13) and African ancestries (rs2066702; p = 2.2E-9).
Significant genetic correlations were observed with 17 phenotypes, including
schizophrenia, ADHD, depression, and use of cigarettes and cannabis. The genetic
underpinnings of AD only partially overlap with those for alcohol consumption,
underscoring the genetic distinction between pathological and non-pathological
drinking behaviors.
Genome-wide association studies (GWASs) have focused primarily on populations of European descent, but it is essential that diverse populations become better represented. Increasing diversity among study participants will advance our understanding of genetic architecture in all populations and ensure that genetic research is broadly applicable. To facilitate and promote research in multiancestry and admixed cohorts, we outline key methodological considerations and highlight opportunities, challenges, solutions, and areas in need of development. Despite the perception that analyzing genetic data from diverse populations is difficult, it is scientifically and ethically imperative, and there is an expanding analytical toolbox to do it well.
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