Familial co-aggregation and shared heritability between clinically diagnosed neurodevelopmental problems and cardiometabolic conditions: a nationwide register study across three generations

Abstract Neurodevelopmental conditions such as attention-deficit/hyperactivity disorder (ADHD) and autism co-occur with cardiometabolic conditions. However, little is known about the mechanisms underlying this co-occurrence. In this nationwide three-generation study using population-based registers in the Netherlands (n=15 million), we assessed the familial (co-)aggregation of ADHD, autism, and cardiometabolic conditions, and estimated their heritabilities and genetic correlations. ADHD, autism, and cardiometabolic conditions showed aggregation and co-aggregation within families and between spouses. Estimated heritabilities of ADHD and autism were moderate (both〖 h〗^2=0.5), while those of cardiometabolic conditions ranged from low to moderate (h^2=0.1-0.4). Genetic correlations between neurodevelopmental and cardiometabolic conditions were modest (r_g=–0.02-0.20). Together, these results suggest a partly shared familial liability for neurodevelopmental and cardiometabolic conditions, and environmental factors likely play a more important role in the co-occurrence of neurodevelopmental and cardiometabolic conditions than genetics. These new insights can advance research toward specific etiological mechanisms and inform preventive strategies.