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

Author:

Hu Shao-Hua,Li Hai-mei,Yu Hao,Liu Yan,Liu Chen-Xing,Zuo Xian-bo,Lu Jing,Jiang Jia-Jun,Xi Cai-Xi,Huang Bo-Chao,Xu Hu-Ji,Hu Jian-Bo,Lai Jian-Bo,Huang Man-Li,Liu Jian-Ning,Xu Dan-Ge,Guo Xi-Chao,Wu Wei,Wu Xin,Jiang Lei,Li Meng,Zhang Guang-Ping,Huang Jin-Wen,Wei Ning,Lv Wen,Duan Jin-Feng,Qi Hong-Li,Hu Chan-Chan,Chen Jing-Kai,Zhou Wei-Hua,Xu Wei-Juan,Liu Chen-Feng,Liang Hai-Yong,Du Jing,Zheng Shu-Fa,Lu Qiao-Ling,Zheng Lin,Hu Xiao-Wei,Chen Feng-Xiang,Chen Peng,Zhu Biao,Xu Li-Jun,Ni Zhi-Min,Fang Ye-Zhen,Yang Zuo-Kai,Shan Xin-Ren,Zheng En-de,Zhang Fan,Zhou Qing-qing,Rao Yi,Swaab Dick,Yue Wei-Hua,Xu YiORCID

Abstract

AbstractEpidemiological 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, Pmeta = 8.36 × 10−8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 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, Pmeta = 1.95 × 10−8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10−9; rs2106525, 7q31.1, MDFIC, Pmeta = 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 homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Genetics,Molecular Biology,Biochemistry

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