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

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...

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Autores principales:	Shao-Hua Hu, Hai-mei Li, Hao Yu, Yan Liu, Chen-Xing Liu, Xian-bo Zuo, Jing Lu, Jia-Jun Jiang, Cai-Xi Xi, Bo-Chao Huang, Hu-Ji Xu, Jian-Bo Hu, Jian-Bo Lai, Man-Li Huang, Jian-Ning Liu, Dan-Ge Xu, Xi-Chao Guo, Wei Wu, Xin Wu, Lei Jiang, Meng Li, Guang-Ping Zhang, Jin-Wen Huang, Ning Wei, Wen Lv, Jin-Feng Duan, Hong-Li Qi, Chan-Chan Hu, Jing-Kai Chen, Wei-Hua Zhou, Wei-Juan Xu, Chen-Feng Liu, Hai-Yong Liang, Jing Du, Shu-Fa Zheng, Qiao-Ling Lu, Lin Zheng, Xiao-Wei Hu, Feng-Xiang Chen, Peng Chen, Biao Zhu, Li-Jun Xu, Zhi-Min Ni, Ye-Zhen Fang, Zuo-Kai Yang, Xin-Ren Shan, En-de Zheng, Fan Zhang, Qing-qing Zhou, Yi Rao, Dick Swaab, Wei-Hua Yue, Yi Xu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Cytology QH573-671
Acceso en línea:	https://doaj.org/article/dee3a730fc384d1d91c8dc40ff55e2da
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spelling	oai:doaj.org-article:dee3a730fc384d1d91c8dc40ff55e2da2021-11-08T11:14:45ZDiscovery of new genetic loci for male sexual orientation in Han population10.1038/s41421-021-00341-72056-5968https://doaj.org/article/dee3a730fc384d1d91c8dc40ff55e2da2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41421-021-00341-7https://doaj.org/toc/2056-5968Abstract 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 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.Shao-Hua HuHai-mei LiHao YuYan LiuChen-Xing LiuXian-bo ZuoJing LuJia-Jun JiangCai-Xi XiBo-Chao HuangHu-Ji XuJian-Bo HuJian-Bo LaiMan-Li HuangJian-Ning LiuDan-Ge XuXi-Chao GuoWei WuXin WuLei JiangMeng LiGuang-Ping ZhangJin-Wen HuangNing WeiWen LvJin-Feng DuanHong-Li QiChan-Chan HuJing-Kai ChenWei-Hua ZhouWei-Juan XuChen-Feng LiuHai-Yong LiangJing DuShu-Fa ZhengQiao-Ling LuLin ZhengXiao-Wei HuFeng-Xiang ChenPeng ChenBiao ZhuLi-Jun XuZhi-Min NiYe-Zhen FangZuo-Kai YangXin-Ren ShanEn-de ZhengFan ZhangQing-qing ZhouYi RaoDick SwaabWei-Hua YueYi XuNature Publishing GrouparticleCytologyQH573-671ENCell Discovery, Vol 7, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Cytology QH573-671
spellingShingle	Cytology QH573-671 Shao-Hua Hu Hai-mei Li Hao Yu Yan Liu Chen-Xing Liu Xian-bo Zuo Jing Lu Jia-Jun Jiang Cai-Xi Xi Bo-Chao Huang Hu-Ji Xu Jian-Bo Hu Jian-Bo Lai Man-Li Huang Jian-Ning Liu Dan-Ge Xu Xi-Chao Guo Wei Wu Xin Wu Lei Jiang Meng Li Guang-Ping Zhang Jin-Wen Huang Ning Wei Wen Lv Jin-Feng Duan Hong-Li Qi Chan-Chan Hu Jing-Kai Chen Wei-Hua Zhou Wei-Juan Xu Chen-Feng Liu Hai-Yong Liang Jing Du Shu-Fa Zheng Qiao-Ling Lu Lin Zheng Xiao-Wei Hu Feng-Xiang Chen Peng Chen Biao Zhu Li-Jun Xu Zhi-Min Ni Ye-Zhen Fang Zuo-Kai Yang Xin-Ren Shan En-de Zheng Fan Zhang Qing-qing Zhou Yi Rao Dick Swaab Wei-Hua Yue Yi Xu Discovery of new genetic loci for male sexual orientation in Han population
description	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 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.
format	article
author	Shao-Hua Hu Hai-mei Li Hao Yu Yan Liu Chen-Xing Liu Xian-bo Zuo Jing Lu Jia-Jun Jiang Cai-Xi Xi Bo-Chao Huang Hu-Ji Xu Jian-Bo Hu Jian-Bo Lai Man-Li Huang Jian-Ning Liu Dan-Ge Xu Xi-Chao Guo Wei Wu Xin Wu Lei Jiang Meng Li Guang-Ping Zhang Jin-Wen Huang Ning Wei Wen Lv Jin-Feng Duan Hong-Li Qi Chan-Chan Hu Jing-Kai Chen Wei-Hua Zhou Wei-Juan Xu Chen-Feng Liu Hai-Yong Liang Jing Du Shu-Fa Zheng Qiao-Ling Lu Lin Zheng Xiao-Wei Hu Feng-Xiang Chen Peng Chen Biao Zhu Li-Jun Xu Zhi-Min Ni Ye-Zhen Fang Zuo-Kai Yang Xin-Ren Shan En-de Zheng Fan Zhang Qing-qing Zhou Yi Rao Dick Swaab Wei-Hua Yue Yi Xu
author_facet	Shao-Hua Hu Hai-mei Li Hao Yu Yan Liu Chen-Xing Liu Xian-bo Zuo Jing Lu Jia-Jun Jiang Cai-Xi Xi Bo-Chao Huang Hu-Ji Xu Jian-Bo Hu Jian-Bo Lai Man-Li Huang Jian-Ning Liu Dan-Ge Xu Xi-Chao Guo Wei Wu Xin Wu Lei Jiang Meng Li Guang-Ping Zhang Jin-Wen Huang Ning Wei Wen Lv Jin-Feng Duan Hong-Li Qi Chan-Chan Hu Jing-Kai Chen Wei-Hua Zhou Wei-Juan Xu Chen-Feng Liu Hai-Yong Liang Jing Du Shu-Fa Zheng Qiao-Ling Lu Lin Zheng Xiao-Wei Hu Feng-Xiang Chen Peng Chen Biao Zhu Li-Jun Xu Zhi-Min Ni Ye-Zhen Fang Zuo-Kai Yang Xin-Ren Shan En-de Zheng Fan Zhang Qing-qing Zhou Yi Rao Dick Swaab Wei-Hua Yue Yi Xu
author_sort	Shao-Hua Hu
title	Discovery of new genetic loci for male sexual orientation in Han population
title_short	Discovery of new genetic loci for male sexual orientation in Han population
title_full	Discovery of new genetic loci for male sexual orientation in Han population
title_fullStr	Discovery of new genetic loci for male sexual orientation in Han population
title_full_unstemmed	Discovery of new genetic loci for male sexual orientation in Han population
title_sort	discovery of new genetic loci for male sexual orientation in han population
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/dee3a730fc384d1d91c8dc40ff55e2da
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Discovery of new genetic loci for male sexual orientation in Han population

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