In:
Cell Discovery, Springer Science and Business Media LLC, Vol. 7, No. 1 ( 2021-10-31)
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.
Type of Medium:
Online Resource
ISSN:
2056-5968
DOI:
10.1038/s41421-021-00341-7
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2021
detail.hit.zdb_id:
2842548-0
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