Association study and mutation sequencing of genes on chromosome 15q11-q13 identified GABRG3 as a susceptibility gene for autism in Chinese Han population.
Association study and mutation sequencing of genes on chromosome 15q11-q13 identified GABRG3 as a susceptibility gene for autism in Chinese Han population.
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染色体15q11-q13基因关联研究及突变测序鉴定GABRG3为中国汉族人群自闭症易感基因
DOI：
10.1038/s41398-018-0197-4
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发表时间：
2018-08-14
影响因子：
6.8
通讯作者：
Wang L
中科院分区：
文献类型：
--
作者：
Wang L;Li J;Shuang M;Lu T;Wang Z;Zhang T;Yue W;Jia M;Ruan Y;Liu J;Wu Z;Zhang D;Wang L
细胞遗传学研究表明，染色体 15q11-q13 可能是增加自闭症风险的候选区域。先前针对白种人群体的关联研究确定了该区域基因的风险变异。然而，这些基因与中国汉族人群自闭症的关系仍不清楚。在此，利用512个自闭症三人组对该区域的41个标签单核苷酸多态性（SNP）进行基于家系的关联研究，以探讨染色体15q11-q13上的蛋白质编码基因与中国汉族人群自闭症之间的关联。此外，我们对这些自闭症相关基因进行了测序，以检测 512 名自闭症三人组和 575 名健康对照者中的罕见变异。我们的结果表明，GABRG3 中 rs7180500 的 C 等位基因是自闭症的风险变异 (p = 0.00057)。表达数量性状位点（eQTL）分析显示rs7180500的C等位基因可能与小脑中GABRG3的表达相关（Braineac：p = 0.0048；GTEx：p = 0.0010）。此外，测序还发现了自闭症患者中GABRG3中的两个罕见变异rs201602655 (p.Val233Met)和rs201427468 (p.Pro365Ser)以及GABRB3中的六个罕见变异。在这些变异中，在 512 名自闭症儿童中的 9 名和 575 名健康对照中的 2 名中观察到了 GABRG3 中的 rs201602655 (p.Val233Met)（Pearson χ2 检验，χ2 = 5.375，p = 0.020）。功能预测表明 rs201602655 (p.Val233Met) 可能是有害的。因此，这些发现表明GABRG3可能与中国汉族人群自闭症的发病机制有关。
Cytogenetic studies suggested that chromosome 15q11-q13 might be a candidate region that increases the risk of autism. Previous association studies in Caucasian populations identified the risk variants of genes in this region. However, the association of these genes with autism in Chinese Han population remains unclear. Herein, 512 autism trios were utilized for a family-based association study of 41 tag single nucleotide polymorphisms (SNPs) in this region to explore the association between protein-coding genes on chromosome 15q11-q13 and autism in Chinese Han population. Furthermore, we sequenced these autism-related genes to detect rare variants in 512 autism trios and 575 healthy controls. Our results showed that the C allele of rs7180500 in GABRG3 was a risk variant for autism (p = 0.00057). The expression quantitative trait loci (eQTL) analysis revealed that the C allele of rs7180500 might be associated with the expression of GABRG3 in the cerebellum (Braineac: p = 0.0048; GTEx: p = 0.0010). Moreover, the sequencing identified two rare variants rs201602655 (p.Val233Met) and rs201427468 (p.Pro365Ser) in GABRG3 and six rare variants in GABRB3 in autistic patients. Among these variants, rs201602655 (p.Val233Met) in GABRG3 were observed in 9 of 512 autistic children and 2 of 575 healthy controls (Pearson χ2-test, χ2 = 5.375, p = 0.020). The functional prediction indicated that rs201602655 (p.Val233Met) might be deleterious. Thus, these findings demonstrated that GABRG3 might contribute to the pathogenesis of autism in Chinese Han population.
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影响因子：
16.2
作者：
Iossifov I;Ronemus M;Levy D;Wang Z;Hakker I;Rosenbaum J;Yamrom B;Lee YH;Narzisi G;Leotta A;Kendall J;Grabowska E;Ma B;Marks S;Rodgers L;Stepansky A;Troge J;Andrews P;Bekritsky M;Pradhan K;Ghiban E;Kramer M;Parla J;Demeter R;Fulton LL;Fulton RS;Magrini VJ;Ye K;Darnell JC;Darnell RB;Mardis ER;Wilson RK;Schatz MC;McCombie WR;Wigler M
通讯作者：
Wigler M
影响因子：
30.8
作者：
Helbig I;Mefford HC;Sharp AJ;Guipponi M;Fichera M;Franke A;Muhle H;de Kovel C;Baker C;von Spiczak S;Kron KL;Steinich I;Kleefuss-Lie AA;Leu C;Gaus V;Schmitz B;Klein KM;Reif PS;Rosenow F;Weber Y;Lerche H;Zimprich F;Urak L;Fuchs K;Feucht M;Genton P;Thomas P;Visscher F;de Haan GJ;Møller RS;Hjalgrim H;Luciano D;Wittig M;Nothnagel M;Elger CE;Nürnberg P;Romano C;Malafosse A;Koeleman BP;Lindhout D;Stephani U;Schreiber S;Eichler EE;Sander T
通讯作者：
Sander T
影响因子：
2.6
作者：
Cellot G;Cherubini E
通讯作者：
Cherubini E
影响因子：
4
作者：
Ben-Shachar S;Lanpher B;German JR;Qasaymeh M;Potocki L;Nagamani SC;Franco LM;Malphrus A;Bottenfield GW;Spence JE;Amato S;Rousseau JA;Moghaddam B;Skinner C;Skinner SA;Bernes S;Armstrong N;Shinawi M;Stankiewicz P;Patel A;Cheung SW;Lupski JR;Beaudet AL;Sahoo T
通讯作者：
Sahoo T
影响因子：
3.5
作者：
Berkel S;Tang W;Treviño M;Vogt M;Obenhaus HA;Gass P;Scherer SW;Sprengel R;Schratt G;Rappold GA
通讯作者：
Rappold GA