Allelic frequency differences of DAOA variants between Caucasians and Asians and their association with major mood disorders

摘要

Major mood disorders, which primarily include bipolar disorder(BD) and major depressive disorder (MDD), are among the mostcommon psychiatric disorders and are recognized as leadingcauses of morbidity worldwide. Family, twin and adoption studieshave consistently indicated moderate-to-strong genetic contributionsto the risk of major mood disorders.1 Genetic association andgenome-wide association studies (GWAS) suggest that there issome degree of overlap for some specific disorders but alsospecific genetic diversity.2 DAOA (D-amino acid oxidase activator),a gene located on human chromosome 13q33.2, plays a crucialrole in the central nervous system through binding with DAO(encoding D-amino acid oxidase). Convergent lines of biologicalevidence suggest that DAOA is an attractive candidate gene formajor mood disorders.2,3 Multiple studies have been conducted tocharacterize the association of DAOA with major mood disordersin diverse populations, but inconsistent results have beenreported.4 The inconsistent associations of SNPs in DAOA withmajor mood disorders may be explained by various studyassertions, ethnic heterogeneity, and insufficient statistical power.Here, we collected all available genetic and phenotypic data fromdiverse samples (including GWASs and candidate gene studies) toperform a systematic meta-analysis of seven SNPs across theDAOA gene locus (65,087 subjects and 1022 nuclear families) andfurther investigate the functional consequence of risk SNPrs2391191 on cis-regulation of DAOA expression and bindingaffinity to transcription factor TCF4.