Genomewide Association Study of Alcohol Dependence and Related Traits in a Thai Population

Background: Alcohol use (both quantity and dependence) is moderately heritable, and genomewide association studies (GWAS) have identified risk genes in European, African, and Asian populations. The most reproducibly identified risk genes affect alcohol metabolism. Well-known functional variants at the gene encoding alcohol dehydrogenase B and other alcohol dehydrogenases affect risk in European and African ancestry populations. Similarly, variants mapped to these same genes and a well-known null variant that maps to the gene that encodes aldehyde dehydrogenase 2 (ALDH2) also affect risk in various Asian populations. In this study, we completed the first GWAS for 3 traits related to alcohol use in a Thai population recruited initially for studies of methamphetamine dependence.

Methods: All subjects were evaluated with the Thai version of the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA). A total of 1,045 subjects were available for analysis. Three traits were analyzed: flushing, maximum number of alcoholic beverages consumed in any lifetime 24-hour period ("MAXDRINKS"), and DSM-IV alcohol dependence criterion count. We also conducted a pleiotropy analysis with major depression, the only other psychiatric trait where summary statistics from a large-scale Asian-population GWAS are available.

Results: All 3 traits showed genomewide significant association with variants near ALDH2, with significance ranging from 2.01 × 10^-14 (for flushing; lead single nucleotide polymorphism (SNP) PTPN11* rs143894582) to p_meta = 5.80 × 10^-10 (for alcohol dependence criterion count; lead SNP rs149212747). These lead SNPs flank rs671 and span a region of over a megabase, illustrating the need for prior biological information in identifying the actual effect SNP, rs671. We also identified significant pleiotropy between major depression and flushing.

Conclusions: These results are consistent with prior findings in Asian populations and add new information regarding alcohol use-depression pleiotropy.