Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs.

ABSTRACT: Traits related to primary and secondary sexual characteristics greatly impact females during puberty and day-to-day adult life. Therefore, we performed a GWAS analysis of 11,348 Japanese female volunteers and 22 gynecology-related phenotypic variables, and identified significant associations for bust-size, menstrual pain (dysmenorrhea) severity, and menstrual fever. Bust-size analysis identified significant association signals in CCDC170-ESR1 (rs6557160; P?=?1.7?×?10-16) and KCNU1-ZNF703 (rs146992477; P?=?6.2?×?10-9) and found that one-third of known European-ancestry associations were also present in Japanese. eQTL data points to CCDC170 and ZNF703 as those signals' functional targets. For menstrual fever, we identified a novel association in OPRM1 (rs17181171; P?=?2.0?×?10-8), for which top variants were eQTLs in multiple tissues. A known dysmenorrhea signal near NGF replicated in our data (rs12030576; P?=?1.1?×?10-19) and was associated with RP4-663N10.1 expression, a putative lncRNA enhancer of NGF, while a novel dysmenorrhea signal in the IL1 locus (rs80111889; P?=?1.9?×?10-16) contained SNPs previously associated with endometriosis, and GWAS SNPs were most significantly associated with IL1A expression. By combining regional imputation with colocalization analysis of GWAS/eQTL signals along with integrated annotation with epigenomic data, this study further refines the sets of candidate causal variants and target genes for these known and novel gynecology-related trait loci.

SUBMITTER: Hirata T 

PROVIDER: S-EPMC5981393 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature