Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs.
Japanese GWAS identifies variants for bust-size, dysmenorrhea, and menstrual fever that are eQTLs for relevant protein-coding or long non-coding RNAs.
复制标题
DOI：
10.1038/s41598-018-25065-9
复制
发表时间：
2018-05-31
影响因子：
4.6
通讯作者：
Osuga Y
中科院分区：
文献类型：
--
作者：
Hirata T;Koga K;Johnson TA;Morino R;Nakazono K;Kamitsuji S;Akita M;Kawajiri M;Kami A;Hoshi Y;Tada A;Ishikawa K;Hine M;Kobayashi M;Kurume N;Fujii T;Kamatani N;Osuga Y
与第一性征和第二性征相关的特征对女性在青春期和成年后的日常生活有很大影响。因此，我们对 11,348 名日本女性志愿者和 22 个妇科相关表型变量进行了 GWAS 分析，发现胸围大小、经痛（痛经）严重程度和经期发热之间存在显着关联。胸围大小分析确定了 CCDC170-ESR1 (rs6557160; P = 1.7 × 10−16) 和 KCNU1-ZNF703 (rs146992477; P = 6.2 × 10−9) 中的显着关联信号，并发现三分之一的已知欧洲血统关联也存在日语。 eQTL 数据指出 CCDC170 和 ZNF703 作为这些信号的功能目标。对于月经热，我们发现了 OPRM1 中的一种新关联（rs17181171；P = 2.0 × 10−8），其中最主要的变异是多个组织中的 eQTL。 NGF 附近已知的痛经信号在我们的数据中复制（rs12030576；P = 1.1 × 10−19），并与 RP4-663N10.1 表达相关，RP4-663N10.1 是 NGF 的推定 lncRNA 增强子，而 IL1 基因座中存在新的痛经信号（rs80111889； P = 1.9 × 10−16)包含先前与子宫内膜异位症相关的SNP，并且GWAS SNP与IL1A表达最显着相关。通过将区域插补与 GWAS/eQTL 信号的共定位分析以及表观基因组数据的集成注释相结合，本研究进一步细化了这些已知和新颖的妇科相关性状位点的候选因果变异和目标基因组。
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.
登录
查看更多内容
Interleukin-1家族：回到未来。
影响因子：
32.4
作者：
Garlanda C;Dinarello CA;Mantovani A
通讯作者：
Mantovani A
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
3.5
作者：
Demerath, Ellen W.;Liu, Ching-Ti;Haiman, Christopher A.
通讯作者：
Haiman, Christopher A.
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
14.9
作者：
Griffon A;Barbier Q;Dalino J;van Helden J;Spicuglia S;Ballester B
通讯作者：
Ballester B