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<p>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 (<i>n</i> = 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 <i>h</i><sup>2</sup> = 0.5), while those of cardiometabolic conditions ranged from low to moderate (<i>h</i><sup>2</sup> = 0.1–0.4). Genetic correlations between neurodevelopmental and cardiometabolic conditions were modest (<i>r</i><sub>g</sub> = –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.</p>

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Familial co-aggregation and shared heritability between neurodevelopmental problems and cardiometabolic conditions

  • 期刊论文

  • 发表日期：

    2025年11月3日

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  • Yiran Li,
  • Yiling Zhou,
  • Melissa Vos,
  • Martje Bos,
  • Olivier Steen,
  • Naomi R. Wray,
  • Catharina A. Hartman,
  • Harold Snieder

摘要

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 h2 = 0.5), while those of cardiometabolic conditions ranged from low to moderate (h2 = 0.1–0.4). Genetic correlations between neurodevelopmental and cardiometabolic conditions were modest (rg = –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.