Discovery of new genetic loci for male sexual orientation in Han population.
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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 Yi
Аннотация
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, 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.