Examining Sex Differences in Autism Heritability

作者：Sven Sandin, Benjamin Hon Kei Yip, Weiyao Yin, Lauren A. Weiss, Joseph D. Dougherty, Stuart B. Fass, John N. Constantino, Zhu Hailin, Tychele N. Turner, Natasha Marrus, David H. Gutmann, Stephan Sanders, Benjamin Christoffersson · 发表于：JAMA Psychiatry · 年份：2024 · DOI：10.1001/jamapsychiatry.2024.0525 · 被引用次数：43 · 研究领域：Autism Spectrum Disorder Research、Family and Disability Support Research、Child Nutrition and Feeding Issues

Importance: Autism spectrum disorder (ASD) is a neurodevelopmental disorder more prevalent in males than in females. The cause of ASD is largely genetic, but the association of genetics with the skewed sex ratio is not yet understood. To our knowledge, no large population-based study has provided estimates of heritability by sex. Objective: To estimate the sex-specific heritability of ASD. Design, Setting, and Participants: This was a population-based, retrospective analysis using national health registers of nontwin siblings and cousins from Sweden born between January 1, 1985, and December 31, 1998, with follow-up to 19 years of age. Data analysis occurred from August 2022 to November 2023. Main Outcomes and Measures: Models were fitted to estimate the relative variance in risk for ASD occurrence owing to sex-specific additive genetics, shared environmental effects, and a common residual term. The residual term conceptually captured other factors that promote individual behavioral variation (eg, maternal effects, de novo variants, rare genetic variants not additively inherited, or gene-environment interactions). Estimates were adjusted for differences in prevalence due to birth year and maternal and paternal age by sex. Results: The sample included 1 047 649 individuals in 456 832 families (538 283 males [51.38%]; 509 366 females [48.62%]). Within the entire sample, 12 226 (1.17%) received a diagnosis of ASD, comprising 8128 (1.51%) males and 4098 (0.80%) females. ASD herit...