The female protective effect against autism spectrum disorder.
The female protective effect against autism spectrum disorder.
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DOI：
10.1016/j.xgen.2022.100134
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发表时间：
2022-06-08
期刊：
影响因子：
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通讯作者：
Robinson, Elise B.
中科院分区：
文献类型：
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作者：
Wigdor, Emilie M.;Weiner, Daniel J.;Grovo, Jako;Fu, Jack M.;Thompson, Wesley K.;Carey, Caitlin E.;Baya, Nikolas;van der Merwe, Celia;Walters, Raymond K.;Satterstrom, F. Kyle;Palmer, Duncan S.;Rosengren, Anders;iPSYCH Consortium, David M.;Hougaard, David M.;Mortensen, Preben Bo;Daily, Mark J.;Talkowski, Michael E.;Sanders, Stephan J.;Bishop, Somer L.;Borglum, Anders D.;Robinson, Elise B.
自闭症谱系障碍(ASD)在男性中被诊断为自闭症谱系障碍(ASD)的频率是女性的三到四倍。对罕见变异的遗传学研究支持女性对ASD的保护作用(FPE)。然而，ASD常见遗传风险的性别差异研究较少，尤其是在家庭内部。利用丹麦的IPSYCH资源，我们发现女性自闭症病例的同胞(n=1,707)的自闭症发病率高于男性自闭症病例的同胞(n=6,270；p<；−10)。在Simons Simplex和Spark集合中，ASD病例的母亲(n=7,436)比ASD病例的父亲携带更多的多基因风险(n=5,926；0.08多基因风险分数[Prs]SD；p=7.0t×10−7)。此外，未受影响的男性兄弟姐妹遗传多基因风险不足(n=1,519；p=0.03)。使用流行病学和遗传学方法，我们的发现有力地支持了针对ASD常见遗传影响的FPE。女性对ASD保护作用的证据来自FPE的常见、遗传变异证据在受ASD影响的家庭成员中，患有ASD儿童的母亲比父亲Wigdor等人携带更多的遗传风险。找到证据支持女性对自闭症谱系障碍(ASD)的保护作用：(1)女性ASD先证者的兄弟姐妹比男性ASD先证者的兄弟姐妹更有可能被诊断为ASD，(2)母亲比父亲携带更常见的ASD遗传风险。综上所述，这些结果强调了性别在ASD风险中的广泛作用，并可能影响ASD遗传和神经生物学研究的设计和解释。
Autism spectrum disorder (ASD) is diagnosed three to four times more frequently in males than in females. Genetic studies of rare variants support a female protective effect (FPE) against ASD. However, sex differences in common inherited genetic risk for ASD are less studied, particularly within families. Leveraging the Danish iPSYCH resource, we found siblings of female ASD cases (n = 1,707) had higher rates of ASD than siblings of male ASD cases (n = 6,270; p < 1.0 × 10−10). In the Simons Simplex and SPARK collections, mothers of ASD cases (n = 7,436) carried more polygenic risk for ASD than fathers of ASD cases (n = 5,926; 0.08 polygenic risk score [PRS] SD; p = 7.0 × 10−7). Further, male unaffected siblings under-inherited polygenic risk (n = 1,519; p = 0.03). Using both epidemiologic and genetic approaches, our findings strongly support an FPE against ASD’s common inherited influences. Evidence of female protective effect against ASD from common, inherited variation Evidence of FPE in both affected and unaffected members of ASD-impacted families Mothers of children with ASD carry more genetic risk for ASDs than fathers Wigdor et al. find evidence supporting a female protective effect against autism spectrum disorder (ASD): (1) siblings of female ASD probands are more likely to be diagnosed with ASD than siblings of male ASD probands and (2) mothers carry more common, inherited genetic risk for ASD than fathers. Taken together, these results emphasize the breadth of the role of sex in ASD risk and could impact the design and interpretation of genetic and neurobiological studies of ASD.
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