A.J. Drexel Autism Institute, Drexel University, Philadelphia, Pennsylvania, USA.
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus, Denmark.
Autism Res. 2024 Oct;17(10):2144-2155. doi: 10.1002/aur.3232. Epub 2024 Sep 16.
The relatively few conditions and family member types (e.g., sibling, parent) considered in investigations of family health history in autism spectrum disorder (ASD, or autism) limits understanding of the role of family history in autism etiology. For more comprehensive understanding and hypothesis-generation, we produced an open-source catalog of autism associations with family histories of mental, neurologic, cardiometabolic, birth defect, asthma, allergy, and autoimmune conditions. All live births in Denmark, 1980-2012, of Denmark-born parents (1,697,231 births), and their 3-generation family members were followed through April 10, 2017 for each of 90 diagnoses (including autism), emigration or death. Adjusted hazard ratios (aHR) were estimated via Cox regression for each diagnosis-family member type combination, adjusting for birth year, sex, birth weight, gestational age, parental ages at birth, and number of family member types of index person; aHRs also calculated for sex-specific co-occurrence of each disorder. We obtained 6462 individual family history aHRS across autism overall (26,840 autistic persons; 1.6% of births), by sex, and considering intellectual disability (ID); and 350 individual co-occurrence aHRS. Results are cataloged in interactive heat maps and down-loadable data files: https://ncrr-au.shinyapps.io/asd-riskatlas/ and interactive graphic summaries: https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots_16918786403110/e-Figure5. While primarily for reference material or use in other studies (e.g., meta-analyses), results revealed considerable breadth and variation in magnitude of familial health history associations with autism by type of condition, family member type, sex of the family member, side of the family, sex of the index person, and ID status, indicative of diverse genetic, familial, and nongenetic autism etiologic pathways. Careful attention to sources of autism likelihood in family health history, aided by our open data resource, may accelerate understanding of factors underlying neurodiversity.
在自闭症谱系障碍（ASD，或自闭症）的家族健康史研究中，相对较少的条件和家庭成员类型（例如，兄弟姐妹、父母）被考虑在内，这限制了对家族史在自闭症发病机制中的作用的理解。为了更全面地理解和产生假说，我们生成了一个自闭症关联的开源目录，其中包括有精神、神经、心血管代谢、出生缺陷、哮喘、过敏和自身免疫疾病家族史的病例。丹麦所有 1980 年至 2012 年出生的、父母均为丹麦出生的活产儿（1697231 例出生）及其三代家庭成员，自 2017 年 4 月 10 日起，每例自闭症患者（包括自闭症）及其家庭成员均通过 Cox 回归进行调整后的危险比（aHR）进行随访，调整因素包括出生年份、性别、出生体重、胎龄、父母出生时的年龄以及索引个体的家庭成员类型数量；还计算了每种疾病的性别特异性共现的 aHR。我们获得了自闭症整体（26840 名自闭症患者；占出生人数的 1.6%）、按性别和考虑智力障碍（ID）的情况下的 6462 个个体家族史 aHR，以及 350 个共现 aHR。结果以交互热图和可下载数据文件的形式进行了分类：https://ncrr-au.shinyapps.io/asd-riskatlas/ 和交互图形摘要：https://public.tableau.com/app/profile/diana.schendel/viz/ASDPlots_16918786403110/e-Figure5。虽然这些结果主要是为了参考材料或用于其他研究（例如，荟萃分析），但结果显示，与自闭症相关的家族健康史的类型、家庭成员类型、家庭成员的性别、家族的一侧、索引个体的性别和 ID 状态，都存在相当大的广度和幅度的差异，这表明了自闭症发病机制中的遗传、家族和非遗传因素的多样性。通过我们的开放数据资源，仔细关注家族健康史中自闭症可能性的来源，可能会加速对神经多样性背后因素的理解。
