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

临床诊断的神经发育问题与心血管代谢疾病之间存在家族聚集性和共同遗传性:一项跨越三代人的全国性登记研究

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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.

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