女性对自闭症谱系障碍的保护作用。
The female protective effect against autism spectrum disorder.
作者信息
Wigdor Emilie M, Weiner Daniel J, Grove Jakob, 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, Bybjerg-Grauholm Jonas, Hougaard David M, Mortensen Preben Bo, Daly Mark J, Talkowski Michael E, Sanders Stephan J, Bishop Somer L, Børglum Anders D, Robinson Elise B
机构信息
Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Wellcome Trust Sanger Institute, Hinxton CB10 1SA, UK.
出版信息
Cell Genom. 2022 Jun 8;2(6):100134. doi: 10.1016/j.xgen.2022.100134.
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). 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). 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.
自闭症谱系障碍（ASD）在男性中的诊断率是女性的三到四倍。对罕见变异的基因研究支持女性对ASD具有保护作用（FPE）。然而，关于ASD常见遗传风险中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ASD病例的兄弟姐妹（n = 1707）患ASD的比例高于男性ASD病例的兄弟姐妹（n = 6270；p < 1.0×10）。在西蒙斯单基因病例集和SPARK数据集中，ASD病例的母亲（n = 7436）比ASD病例的父亲（n = 5926；多基因风险评分[PRS]标准差为0.08；p = 7.0×10）携带更多的ASD多基因风险。此外，未受影响的男性兄弟姐妹遗传的多基因风险较低（n = 1519；p = 0.03）。通过流行病学和遗传学方法，我们的研究结果有力地支持了女性对ASD常见遗传影响的保护作用。
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