Genome-Wide Linkage and Association Study of Childhood Gender Nonconformity in Males.
Genome-Wide Linkage and Association Study of Childhood Gender Nonconformity in Males.
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DOI：
10.1007/s10508-021-02146-x
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发表时间：
2021-11
影响因子：
3.8
通讯作者：
Martin ER
中科院分区：
文献类型：
--
作者：
Sanders AR;Beecham GW;Guo S;Dawood K;Rieger G;Krishnappa RS;Kolundzija AB;Bailey JM;Martin ER
男性的性取向受环境和复杂的遗传因素的影响。儿童期性别不一致（CGN）是同性恋与实质性家庭关系的最强相关性之一。我们研究了有两个或更多同性恋兄弟的家庭中的兄弟（384个家庭中的409对和谐兄弟姐妹，以及他们的异性恋兄弟），他们自我回忆了他们的CGN。为了绘制CGN的基因座，我们使用SNP基因型进行了全基因组连锁扫描（GWLS）。最强的连锁峰位于染色体5 q31上，每个连锁峰都具有显著或暗示性的两点LOD得分和多点LOD得分支持（最大两点LOD = 4.45），6 q12（最大两点LOD = 3.64），7 q33（最大两点LOD = 3.09）和8 q24（最大两点LOD = 3.67），与后者不重叠与先前报道的最强的连锁区域的男性性取向的近着丝粒染色体8。基于家族的关联分析用于识别连锁区域中的相关变体，在5 q31连锁峰处发现了一簇SNP（最小关联p = 1.3 × 10-8）。在染色体5 p13、5 q31、7 q32、8 p22和10 q23处发现了在10-6至10-8 p值范围内的全基因组多个SNP簇，突出了谷氨酸相关基因。这是首次报道的CGN的GWLS和全基因组关联研究。进一步增加关于CGN及其与男性性取向关系的遗传知识，应该有助于我们进一步了解这些相关特征的生物学。在线版本包含补充材料，可通过10.1007/s10508-021-02146-x获得。
Male sexual orientation is influenced by environmental and complex genetic factors. Childhood gender nonconformity (CGN) is one of the strongest correlates of homosexuality with substantial familiality. We studied brothers in families with two or more homosexual brothers (409 concordant sibling pairs in 384 families, as well as their heterosexual brothers), who self-recalled their CGN. To map loci for CGN, we conducted a genome-wide linkage scan (GWLS) using SNP genotypes. The strongest linkage peaks, each with significant or suggestive two-point LOD scores and multipoint LOD score support, were on chromosomes 5q31 (maximum two-point LOD = 4.45), 6q12 (maximum two-point LOD = 3.64), 7q33 (maximum two-point LOD = 3.09), and 8q24 (maximum two-point LOD = 3.67), with the latter not overlapping with previously reported strongest linkage region for male sexual orientation on pericentromeric chromosome 8. Family-based association analyses were used to identify associated variants in the linkage regions, with a cluster of SNPs (minimum association p = 1.3 × 10–8) found at the 5q31 linkage peak. Genome-wide, clusters of multiple SNPs in the 10–6 to 10–8 p-value range were found at chromosomes 5p13, 5q31, 7q32, 8p22, and 10q23, highlighting glutamate-related genes. This is the first reported GWLS and genome-wide association study on CGN. Further increasing genetic knowledge about CGN and its relationships to male sexual orientation should help advance our understanding of the biology of these associated traits. The online version contains supplementary material available at 10.1007/s10508-021-02146-x.
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影响因子：
56.9
作者：
Ganna, Andrea;Verweij, Karin J. H.;Wilson, C. H.
通讯作者：
Wilson, C. H.
影响因子：
3.8
作者：
BAILEY, JM;NOTHNAGEL, J;WOLFE, M
通讯作者：
WOLFE, M
影响因子：
30.8
作者：
Abecasis, GR;Cherny, SS;Cardon, LR
通讯作者：
Cardon, LR
影响因子：
17.7
作者：
Kendler, KS;Thornton, LM;Kessler, RC
通讯作者：
Kessler, RC
影响因子：
2.6
作者：
Kirk, KM;Bailey, JM;Martin, NG
通讯作者：
Martin, NG