Discovery of new genetic loci for male sexual orientation in Han population

作者：Shaohua Hu, Haimei Li, Hao Yu, Yan Liu, Chen-Xing Liu, Xian-bo Zuo, Jing Lü, Jiajun Jiang, Cai-Xi Xi, Bochao Huang, Huji Xu, Jianbo Hu, Jianbo Lai, Manli Huang, Jian‐Ning Liu, Dan-Ge Xu, Xichao Guo, Wei Wu, Xin Wu, Lei Jiang, Meng Li, Guangping Zhang, Jinwen Huang, Ning Wei, Wen Lv, Jinfeng Duan, Hongli Qi, Chanchan Hu, Jingkai Chen, Weihua Zhou, Weijuan Xu, Chen–Feng Liu, Haiyong Liang, Jing Du, Shufa Zheng, Lu Qiaoling, Lin Zheng, Xiaowei Hu, Fengxiang Chen, Peng Chen, Biao Zhu, Lijun Xu, Zhimin Ni, Yezhen Fang, Zuo-Kai Yang, Xin-Ren Shan, En-de Zheng, Fan Zhang, Qingqing Zhou, Yi Rao, Dick F. Swaab, Weihua Yue, Yi Xu · 发表于：Cell Discovery · 年份：2021 · DOI：10.1038/s41421-021-00341-7 · 被引用次数：16 · 研究领域：Genetic Associations and Epidemiology、Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities、Genetic and phenotypic traits in livestock

Abstract Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB , P meta = 8.36 × 10 −8 , OR = 1.29; rs7259428, 19q12, ZNF536 , P meta = 7.58 × 10 −8 , OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese ( n = 4791) and European ancestries ( n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1 , P meta = 1.95 × 10 −8 ; rs2414487, 15q21.3, LOC145783 , P meta = 4.53 × 10 −9 ; rs2106525, 7q31.1, MDFIC , P meta = 6.24 × 10 −9 ). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the hom...