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

Sci Rep. 2018 May 31;8(1):8502. doi: 10.1038/s41598-018-25065-9.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Carrier Proteins / genetics
  • Dysmenorrhea / epidemiology
  • Dysmenorrhea / genetics*
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Japan / epidemiology
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci*
  • RNA, Long Noncoding / genetics*
  • Receptors, Opioid, mu / genetics


  • CCDC170 protein, human
  • Carrier Proteins
  • OPRM1 protein, human
  • RNA, Long Noncoding
  • Receptors, Opioid, mu
  • ZNF703 protein, human