Scientific Reports (May 2018)

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

  • Tetsuya Hirata,
  • Kaori Koga,
  • Todd A. Johnson,
  • Ryoko Morino,
  • Kazuyuki Nakazono,
  • Shigeo Kamitsuji,
  • Masanori Akita,
  • Maiko Kawajiri,
  • Azusa Kami,
  • Yuria Hoshi,
  • Asami Tada,
  • Kenichi Ishikawa,
  • Maaya Hine,
  • Miki Kobayashi,
  • Nami Kurume,
  • Tomoyuki Fujii,
  • Naoyuki Kamatani,
  • Yutaka Osuga

DOI
https://doi.org/10.1038/s41598-018-25065-9
Journal volume & issue
Vol. 8, no. 1
pp. 1 – 17

Abstract

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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.