Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) are highly heritable neurodevelopmental disorders that frequently co-occur. Both rare and common genetic variants are important for ASD and ADHD risk but their combined contribution to clinical heterogeneity is unclear. In a sample of 39 ASD and/or ADHD families we estimated the overall variance explained by known rare copy number variants (CNVs) and polygenic risk score (PRS) from common variants to be 10% in comorbid ASD/ADHD, 4% in ASD and 2% in ADHD. We show that burden of large, rare CNVs and PRS is significantly higher in adult ASD and/or ADHD patients with sustained need for specialist care compared to their unaffected relatives, while affected relatives fall in-between the two.

自闭症谱系障碍（ASD）和注意缺陷多动障碍（ADHD）是高度可遗传的神经发育障碍，经常同时发生。稀有和常见的遗传变异对ASD和ADHD风险均很重要，但它们对临床异质性的综合贡献尚不清楚。在39个ASD和/或ADHD家族的样本中，我们估计由常见变体的已知稀有拷贝数变异（CNV）和多基因风险评分（PRS）解释的总体差异在合并症ASD / ADHD中为10％，在ASD中为4％和2％的注意力缺陷多动症。我们显示，与未受影响的亲戚相比，持续需要专业护理的成人ASD和/或ADHD患者中，大型，罕见CNV和PRS的负担明显更高，而受影响的亲属介于两者之间。