Open AccessGenomic Characteristics of Gender Dysphoria Patients and Identification of Rare Mutations in RYR3 Gene
Author(s) -
Fusheng Yang,
Zhu Xiao-hai,
Qing Zhang,
Ning Sun,
Yixuan Ji,
Jinzhao Ma,
Bao Xiao,
Huaiyu Ding,
Shuhan Sun,
Wen Li
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-08655-x
Subject(s) - nonsynonymous substitution , genetics , gene , gene ontology , exome sequencing , biology , mutation , gender dysphoria , genome , gene expression , psychology , gender identity , social psychology
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.