SU33 - A GENOME-WIDE ASSOCIATION STUDY IDENTIFIES A NOVEL LOCUS ASSOCIATED WITH DEPRESSIVE STATE IN THE JAPANESE POPULATION.

Major Depressive Disorder (MDD) is a common and disabling psychiatric disorder. MDD is a multifactorial disorder with multiple genetic and environmental factors with relatively small effects. To date, only a small number of loci have been identified to be significantly (P < 5.0E-8) associated with MDD. To further understand of the genetic basis of MDD, we conducted a Genome-Wide Association Study (GWAS) in East Asia with more than ten thousand participants of Japanese ancestry. Participants completed a self-administered questionnaire on their medical history and health conditions that included the 6-item Kessler screening scale (K6) for depressive state (cut-off point 4/5; 4,071, depressive group [cases]; 6,749, non-depressive group [controls]). The genomic DNA of the participants was extracted from saliva and was genotyped for Single-Nucleotide Polymorphisms (SNPs) using Illumina HumanCore BeadChip (about 300,000 SNPs with add-on 5,000 SNPs). SNPs were excluded if the call rate was < 90%, the minor allele frequency (MAF) was < 1%, or if the Hardy-Weinberg equilibrium P values were < 0.001. A total of 229,276 SNPs from 10,892 individuals were used. We sought for depressive state susceptibility loci and their closest genes. A genome-wide significant association (P=8.8E-9) was observed for a locus in chromosome 20, upstream of WAP-type four-disulfide core 10B (WFDC10B), a member of the WFDC domain family, which has been reported to play a regulatory role in inflammation. On the other hand, there were no SNPs with genome-wide significant associations with past medical history of MDD (898, diagnosed group [cases]; 9,992, non-diagnosed group [controls]). This is, to the best of our knowledge, the first large-scale GWAS using data from direct-to-consumer (DTC) genetic tests carried out in a population not of European-ancestry. The present study detected a novel locus significantly associated with depressive state, but further research is necessary to replicate the current findings. This study suggests that DTC genetic tests with self-reported trait data can contribute to revealing genetic basis for MDD. [ABSTRACT FROM AUTHOR]