Birth order and disease risk across the human phenome - Nature Health

Massive Study of 10 Million Siblings Links Birth Order To Risk of ADHD, Autism

The order matters.ScienceAlert stories are written, fact-checked, and edited by humans, never generated by AI. Don't miss a story, subscribe here.

Older or younger sibling? Birth order may affect health later in life

The order in which children are born may shape their risk of developing dozens of diseases, from autism and allergies to substance abuse.

Whether you are first-born or not may influence what diseases you get

Study suggests first-born children are more likely to develop neurological conditions and second-born are more prone to substance abuse

Birth order and disease risk across the human phenome

Birth-order effects on disease risk have been studied for individual conditions but have not been systematically assessed at phenome-wide scale in large sibling claims cohorts. We apply two complementary designs, a between-family matched cohort (1.6 million pairs) as a high-powered phenome-wide scan, and a within-family sibling comparison (5.1 million families) as an internally controlled sibling contrast, to 569 diseases in Merative MarketScan claims data. Of 418 diseases with adequate case counts, 150 show Bonferroni-significant associations. First-borns carry excess risk for neurodevelopmental conditions (other/unspecified pervasive-developmental-disorder (PDD) code group odds ratio (OR) = 0.57, autism OR = 0.74, attention-deficit/hyperactivity disorder OR = 0.93) and immune-allergic diseases (food allergy OR = 0.80, allergic rhinitis OR = 0.91); second-borns for substance abuse (OR = 1.19) and gastrointestinal conditions (gastritis/duodenitis OR = 1.14). Across diseases analyzed in both designs, between-family and within-family estimates were positively correlated (r = 0.66; 74.2% directionally concordant); 84.7% of Bonferroni-significant between-family hits agreed in direction. Results are robust to state fixed effects (r > 0.99), full-sibling restriction and stricter clinical rematching (r = 0.93). These findings provide a comprehensive map of birth-order effects in the human disease phenome. In multiple study designs involving millions of matched individuals, either between or within families, birth order determined differential associations with disease risk across 569 diseases.

Birth order may influence your disease risk later in life, study finds

Whether you are first-born or second-born may be associated with your risk of developing certain diseases, according to a new study published in Nature Health.