Background

Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood.

Methods

We did a register study in Sweden and identified full-sibling and maternal half-sibling pairs born between Jan 1, 1932, and Dec 31, 1995, through the Population and Multi-Generation Registers. We excluded individuals who died or emigrated before Jan 1, 2005, and included full-siblings who were not twins and did not have half-siblings. ICD diagnoses were obtained from the National Patient Register. We extracted ICD diagnoses for physical conditions, when participants were aged 18 years or older, from inpatient (recorded 1973–2013) and outpatient (recorded 2001–13) services. Diagnoses were regarded as lifetime presence or absence. Logistic regression models were used to estimate the associations between ADHD (exposure) and 35 physical conditions (outcomes) in individuals and across sibling pairs. Quantitative genetic modelling was used to estimate the extent to which genetic and environmental factors accounted for the associations with ADHD.

Findings

4 789 799 individuals were identified (2 449 146 [51%] men and 2 340 653 [49%] women), who formed 4 288 451 unique sibling pairs (3 819 207 full-sibling pairs and 469 244 maternal half-sibling pairs) and 1 841 303 family clusters (siblings, parents, cousins, spouses). The mean age at end of follow-up was 47 years (range 18–81; mean birth year 1966); ethnicity data were not available. Adults with ADHD had increased risk for most physical conditions (34 [97%] of 35) compared with adults without ADHD; the strongest associations were with nervous system disorders (eg, sleep disorders, epilepsy, dementia; odds ratios [ORs] 1·50–4·62) and respiratory diseases (eg, asthma, chronic obstructive pulmonary disease; ORs 2·42–3·24). Sex-stratified analyses showed similar patterns of results in men and women. Stronger cross-disorder associations were found between full-siblings than between half-siblings for nervous system, respiratory, musculoskeletal, and metabolic diseases (p<0·007). Quantitative genetic modelling showed that these associations were largely explained by shared genetic factors (60–69% of correlations), except for associations with nervous system disorders, which were mainly explained by non-shared environmental factors.

Interpretation

This mapping of aetiological sources of cross-disorder overlap can guide future research aiming to identify specific mechanisms contributing to risk of physical conditions in people with ADHD, which could ultimately inform preventive and lifestyle intervention efforts. Our findings highlight the importance of assessing the presence of physical conditions in patients with ADHD.

Funding

Swedish Research Council; Swedish Brain Foundation; Swedish Research Council for Health, Working Life, and Welfare; Stockholm County Council; StratNeuro; EU Horizon 2020 research and innovation programme; National Institute of Mental Health.

中文翻译：

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绘制瑞典 ADHD 与成年身体状况之间的表型和病因学关联：一项遗传信息登记研究

 背景

新的证据表明，多动症患者出现多种身体健康状况的风险增加。只有少数身体状况与多动症的关系得到了彻底的研究，尤其是对老年人的关联知之甚少。我们的目的是调查 ADHD 与成年期各种身体健康状况之间的表型和病因学关联。

 方法

我们在瑞典进行了一项登记研究，通过人口和多代登记册确定了出生于 1932 年 1 月 1 日至 1995 年 12 月 31 日之间的同父异母兄弟姐妹。我们排除了 2005 年 1 月 1 日之前死亡或移居国外的个人，并且包括非双胞胎且没有同父异母兄弟姐妹的全兄弟姐妹。 ICD 诊断是从国家患者登记处获得的。当参与者年龄为 18 岁或以上时，我们从住院（1973-2013 年记录）和门诊（2001-13 年记录）服务中提取了针对身体状况的 ICD 诊断。诊断被视为终生存在或缺席。 Logistic 回归模型用于估计个体和兄弟姐妹之间的 ADHD（暴露）与 35 种身体状况（结果）之间的关联。定量遗传模型用于估计遗传和环境因素与 ADHD 关联的程度。

 发现

确定了 4 789 799 个人（2 449 146 [51%] 男性和 2 340 653 [49%] 女性），他们形成了 4 288 451 个独特的兄弟姐妹对（3 819 207 个全兄弟姐妹对和 469 244 个母亲同父异母兄弟姐妹对） ）和 1 841 303 个家庭群（兄弟姐妹、父母、表兄弟姐妹、配偶）。随访结束时的平均年龄为 47 岁（范围 18-81；平均出生年份 1966 年）；没有种族数据。与没有 ADHD 的成年人相比，患有 ADHD 的成年人大多数身体状况的风险都会增加（35 人中有 34 人 [97%]）；最强的关联是与神经系统疾病（例如，睡眠障碍、癫痫、痴呆；比值比 [OR] 1·50–4·62）和呼吸系统疾病（例如，哮喘、慢性阻塞性肺病；OR 2·42–3） ·24）。性别分层分析显示男性和女性的结果相似。在神经系统、呼吸系统、肌肉骨骼和代谢疾病方面，同父异母兄弟姐妹之间的跨疾病关联性强于同父异母兄弟姐妹之间的关联性（p<0·007）。定量遗传模型表明，这些关联在很大程度上是由共享的遗传因素（60-69%的相关性）来解释的，但与神经系统疾病的关联除外，神经系统疾病的关联主要是由非共享的环境因素来解释的。

 解释

这种跨疾病重叠的病因学来源的映射可以指导未来的研究，旨在确定导致多动症患者身体状况风险的具体机制，这最终可以为预防和生活方式干预工作提供信息。我们的研究结果强调了评估多动症患者身体状况的重要性。

 资金

瑞典研究委员会；瑞典大脑基金会；瑞典健康、工作生活和福利研究委员会；斯德哥尔摩郡议会；策略神经；欧盟地平线2020研究与创新计划；国家心理健康研究所。