Sibling Recurrence Risk and Cross-aggregation of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

Miller M1, Musser ED2, Young GS1, Olson B3, Steiner RD3,4, Nigg JT5,6.

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Abstract

IMPORTANCE:

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are believed to partially share genetic factors and biological influences. As the number of children with these diagnoses rises, so does the number of younger siblings at presumed risk for ADHD and ASD; reliable recurrence risk estimates within and across diagnoses may aid screening and early detection efforts and enhance understanding of potential shared causes.

OBJECTIVE:

To examine within-diagnosis sibling recurrence risk and sibling cross-aggregation of ADHD and ASD among later-born siblings of children with either disorder.

DESIGN, SETTING, AND PARTICIPANTS:

Using data extracted from medical records of 2 large health care systems in the United States, estimates of recurrence risk and cross-aggregation in later-born siblings of children with ADHD or ASD were compared with later-born siblings of children without these diagnoses. One data set included children seen between January 1, 1995, and December 31, 2013; the other included children born between January 1, 1998, and May 17, 2010. Participants included 15 175 later-born siblings of children with ADHD, ASD, and no known diagnosis. The study was conducted from October 2, 2017, to August 14, 2018.

MAIN OUTCOMES AND MEASURES:

Diagnoses of ASD or ADHD in the later-born sibling, ascertained from medical records, were the primary outcomes of interest; moderators included sex, gestational age, and maternal age.

RESULTS:

A total of 15 175 later-born siblings were classified by familial risk status based on the older child's diagnostic status: ADHD risk (n = 730; male [51.92%]), ASD risk (n = 158; male [48.10%]), and no known risk (n = 14 287; male [50.73%]). Compared with later-born siblings of children without ADHD or ASD, later-born siblings of children with ASD were more likely to be diagnosed with ASD (odds ratio [OR], 30.38; 95% CI, 17.73-52.06) or ADHD in the absence of ASD (OR, 3.70; 95% CI, 1.67-8.21). Compared with later-born siblings of children without a diagnosis, later-born siblings of children with ADHD were more likely to be diagnosed with ADHD (OR, 13.05; 95% CI, 9.86-17.27) or ASD in the absence of ADHD (OR, 4.35; 95% CI, 2.43-7.79).

CONCLUSIONS AND RELEVANCE:

Later-born siblings of children with ASD or ADHD appear to be at elevated risk for the same disorder, but also of being diagnosed with the other disorder. These findings provide further support for shared familial mechanisms underlying ASD and ADHD, which may be useful for genetic and prospective developmental studies. Later-born siblings of children with ADHD or ASD should be monitored for both conditions.