Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene

Abstract Gender dysphoria (GD) is characterized by an incongruence between the gender assigned at birth and the gender with which one identifies. The biological mechanisms of GD are unclear. While common genetic variants are associated with GD, positive findings have not always been replicated. To e...

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Autores principales:	Fu Yang, Xiao-hai Zhu, Qing Zhang, Ning-xia Sun, Yi-xuan Ji, Jin-zhao Ma, Bang Xiao, Hai-xia Ding, Shu-han Sun, Wen Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/e93418d59db94b5a8db1192181117c88
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spelling	oai:doaj.org-article:e93418d59db94b5a8db1192181117c882021-12-02T16:06:48ZGenomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene10.1038/s41598-017-08655-x2045-2322https://doaj.org/article/e93418d59db94b5a8db1192181117c882017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08655-xhttps://doaj.org/toc/2045-2322Abstract Gender dysphoria (GD) is characterized by an incongruence between the gender assigned at birth and the gender with which one identifies. The biological mechanisms of GD are unclear. While common genetic variants are associated with GD, positive findings have not always been replicated. To explore the role of rare variants in GD susceptibility within the Han Chinese population, whole-genome sequencing of 9 Han female-to-male transsexuals (FtMs) and whole-exome sequencing of 4 Han male-to-female transsexuals (MtFs) were analyzed using a pathway burden analysis in which variants are first collapsed at the gene level and then by Gene Ontology terms. Novel nonsynonymous variants in ion transport genes were significantly enriched in FtMs (P- value, 2.41E-10; Fold enrichment, 2.8) and MtFs (P- value, 1.04E-04; Fold enrichment, 2.3). Gene burden analysis comparing 13 GD cases and 100 controls implicated RYR3, with three heterozygous damaging mutations in unrelated FtMs and zero in controls (P = 0.001). Importantly, protein structure modeling of the RYR3 mutations indicated that the R1518H mutation made a large structural change in the RYR3 protein. Overall, our results provide information about the genetic basis of GD.Fu YangXiao-hai ZhuQing ZhangNing-xia SunYi-xuan JiJin-zhao MaBang XiaoHai-xia DingShu-han SunWen LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Fu Yang Xiao-hai Zhu Qing Zhang Ning-xia Sun Yi-xuan Ji Jin-zhao Ma Bang Xiao Hai-xia Ding Shu-han Sun Wen Li Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene
description	Abstract Gender dysphoria (GD) is characterized by an incongruence between the gender assigned at birth and the gender with which one identifies. The biological mechanisms of GD are unclear. While common genetic variants are associated with GD, positive findings have not always been replicated. To explore the role of rare variants in GD susceptibility within the Han Chinese population, whole-genome sequencing of 9 Han female-to-male transsexuals (FtMs) and whole-exome sequencing of 4 Han male-to-female transsexuals (MtFs) were analyzed using a pathway burden analysis in which variants are first collapsed at the gene level and then by Gene Ontology terms. Novel nonsynonymous variants in ion transport genes were significantly enriched in FtMs (P- value, 2.41E-10; Fold enrichment, 2.8) and MtFs (P- value, 1.04E-04; Fold enrichment, 2.3). Gene burden analysis comparing 13 GD cases and 100 controls implicated RYR3, with three heterozygous damaging mutations in unrelated FtMs and zero in controls (P = 0.001). Importantly, protein structure modeling of the RYR3 mutations indicated that the R1518H mutation made a large structural change in the RYR3 protein. Overall, our results provide information about the genetic basis of GD.
format	article
author	Fu Yang Xiao-hai Zhu Qing Zhang Ning-xia Sun Yi-xuan Ji Jin-zhao Ma Bang Xiao Hai-xia Ding Shu-han Sun Wen Li
author_facet	Fu Yang Xiao-hai Zhu Qing Zhang Ning-xia Sun Yi-xuan Ji Jin-zhao Ma Bang Xiao Hai-xia Ding Shu-han Sun Wen Li
author_sort	Fu Yang
title	Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene
title_short	Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene
title_full	Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene
title_fullStr	Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene
title_full_unstemmed	Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene
title_sort	genomic characteristics of gender dysphoria patients and identification of rare mutations in ryr3 gene
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/e93418d59db94b5a8db1192181117c88
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Genomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene

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