Brikell Isabell, Wimberley Theresa, Albiñana Clara, Vilhjálmsson Bjarni Jóhann, Agerbo Esben, Børglum Anders D, Demontis Ditte, Schork Andrew J, LaBianca Sonja, Werge Thomas, Hougaard David M, Nordentoft Merete, Mors Ole, Mortensen Preben Bo, Petersen Liselotte Vogdrup, Dalsgaard Søren
iPSYCH-Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen and Aarhus, Denmark (all authors); National Center for Register-Based Research, Department of Economics and Business Economics, Aarhus University, Aarhus, Denmark (Brikell, Wimberley, Albiñana, Vilhjálmsson, Agerbo, Mortensen, Petersen, Dalsgaard); Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Brikell); Center for Integrated Register-Based Research-CIRRAU, Aarhus University, Aarhus, Denmark (Wimberley, Agerbo, Mortensen, Dalsgaard); Bioinformatics Research Center, Aarhus University, Aarhus, Denmark (Vilhjálmsson); Department of Biomedicine and Center for Integrative Sequencing, iSEQ, Aarhus University, Aarhus, Denmark (Børglum, Demontis); Center for Genomics and Personalized Medicine, Central Region Denmark and Aarhus University, Aarhus, Denmark (Børglum, Demontis); Neurogenomics Division, Translational Genomics Research Institute, Phoenix (Schork); Institute of Biological Psychiatry, Mental Health Center Sct. Hans, Mental Health Services Copenhagen, Roskilde, Denmark (Schork, LaBianca, Werge, Nordentoft); Department of Clinical Medicine, University of Copenhagen, Copenhagen (Werge); Center for GeoGenetics, GLOBE Institute, University of Copenhagen, Copenhagen (Werge); Department for Congenital Disorders, Statens Serum Institut, Copenhagen (Hougaard); Copenhagen Research Center for Mental Health, Mental Health Services-CORE in the Capital Region of Denmark (Nordentoft); Psychosis Research Unit, Aarhus University Hospital-Psychiatry, Denmark (Mors).
Am J Psychiatry. 2023 Jan 1;180(1):73-88. doi: 10.1176/appi.ajp.21111105. Epub 2022 Sep 7.
Attention deficit hyperactivity disorder (ADHD) is a multifactorial neurodevelopmental disorder, yet the interplay between ADHD polygenic risk scores (PRSs) and other risk factors remains relatively unexplored. The authors investigated associations, confounding, and interactions of ADHD PRS with birth-related, somatic, and psychosocial factors previously associated with ADHD.
Participants included a random general population sample (N=21,578) and individuals diagnosed with ADHD (N=13,697) from the genotyped Danish iPSYCH2012 case cohort, born between 1981 and 2005. The authors derived ADHD PRSs and identified 24 factors previously associated with ADHD using national registers. Logistic regression was used to estimate associations of ADHD PRS with each risk factor in the general population. Cox models were used to evaluate confounding of risk factor associations with ADHD diagnosis by ADHD PRS and parental psychiatric history, and interactions between ADHD PRS and each risk factor.
ADHD PRS was associated with 12 of 24 risk factors (odds ratio range, 1.03-1.30), namely, small gestational age, infections, traumatic brain injury, and most psychosocial risk factors. Nineteen risk factors were associated with ADHD diagnosis (odds ratio range, 1.20-3.68), and adjusting for ADHD PRS and parental psychiatric history led to only minor attenuations. Only the interaction between ADHD PRS and maternal autoimmune disease survived correction for multiple testing.
Higher ADHD PRS in the general population is associated with small increases in risk for certain birth-related and somatic ADHD risk factors, and broadly to psychosocial adversity. Evidence of gene-environment interaction was limited, as was confounding by ADHD PRS and family psychiatric history on ADHD risk factor associations. This suggests that the majority of the investigated ADHD risk factors act largely independently of current ADHD PRS to increase risk of ADHD.
注意缺陷多动障碍（ADHD）是一种多因素神经发育障碍，但ADHD多基因风险评分（PRSs）与其他风险因素之间的相互作用仍相对未被探索。作者研究了ADHD PRS与先前与ADHD相关的出生相关、躯体和心理社会因素之间的关联、混杂和相互作用。
参与者包括来自1981年至2005年出生的基因分型丹麦iPSYCH2012病例队列的随机普通人群样本（N = 21,578）和被诊断为ADHD的个体（N = 13,697）。作者得出ADHD PRS，并使用国家登记册确定了24个先前与ADHD相关的因素。逻辑回归用于估计普通人群中ADHD PRS与每个风险因素的关联。Cox模型用于评估ADHD PRS和父母精神病史对ADHD诊断的风险因素关联的混杂作用，以及ADHD PRS与每个风险因素之间的相互作用。
ADHD PRS与24个风险因素中的12个相关（优势比范围为1.03 - 1.30），即孕周小、感染、创伤性脑损伤以及大多数心理社会风险因素。19个风险因素与ADHD诊断相关（优势比范围为1.20 - 3.68），对ADHD PRS和父母精神病史进行调整仅导致轻微减弱。只有ADHD PRS与母亲自身免疫性疾病之间的相互作用在多重检验校正后仍然显著。
普通人群中较高的ADHD PRS与某些出生相关和躯体ADHD风险因素的风险小幅增加相关，并广泛与心理社会逆境相关。基因 - 环境相互作用的证据有限，ADHD PRS和家族精神病史对ADHD风险因素关联的混杂作用也有限。这表明大多数研究的ADHD风险因素在很大程度上独立于当前的ADHD PRS起作用，以增加ADHD的风险。
