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Familial liability to Epilepsy and ADHD: A Nationwide Cohort Study
Biological Psychiatry ( IF 10.6 ) Pub Date : 2018-01-01 , DOI: 10.1016/j.biopsych.2017.08.006
Isabell Brikell 1 , Laura Ghirardi 1 , Brian M D'Onofrio 2 , David W Dunn 3 , Catarina Almqvist 4 , Søren Dalsgaard 5 , Ralf Kuja-Halkola 1 , Henrik Larsson 6
Affiliation  

BACKGROUND Epilepsy and attention-deficit/hyperactivity disorder (ADHD) are strongly associated; however, the underlying factors contributing to their co-occurrence remain unclear. A shared genetic liability has been proposed as one possible mechanism. Therefore, our goal in this study was to investigate the familial coaggregation of epilepsy and ADHD and to estimate the contribution of genetic and environmental risk factors to their co-occurrence. METHODS We identified 1,899,654 individuals born between 1987 and 2006 via national Swedish registers and linked each individual to his or her biological relatives. We used logistic regression to estimate the association between epilepsy and ADHD within individual and across relatives. Quantitative genetic modeling was used to decompose the cross-disorder covariance into genetic and environmental factors. RESULTS Individuals with epilepsy had a statistically significant increased risk of ADHD (odds ratio [OR] = 3.47, 95% confidence interval [CI] = 3.33-3.62). This risk increase extended to children whose mothers had epilepsy (OR = 1.85, 95% CI = 1.75-1.96), children whose fathers had epilepsy (OR = 1.64, 95% CI = 1.54-1.74), full siblings (OR = 1.56, 95% CI = 1.46-1.67), maternal half siblings (OR = 1.28, 95% CI = 1.14-1.43), paternal half siblings (OR = 1.10, 95% CI = 0.96-1.25), and cousins (OR = 1.15, 95% CI = 1.10-1.20). The genetic correlation was 0.21 (95% CI = 0.02-0.40) and explained 40% of the phenotypic correlation between epilepsy and ADHD, with the remaining variance largely explained by nonshared environmental factors (49%, nonshared environmental correlation = 0.36, 95% CI = 0.23-0.49). The contribution of shared environmental factors to the cross-disorder overlap was not statistically significant (11%, shared environmental correlation = 0.32, 95% CI = -0.16-0.79). CONCLUSIONS This study demonstrates a strong and etiologically complex association between epilepsy and ADHD, with shared familial factors and risk factors unique to the individual contributing to co-occurrence of the disorders. Our findings suggest that epilepsy and ADHD may share less genetic risk as compared with other neurodevelopmental disorders.

中文翻译:

癫痫和多动症的家族责任:一项全国队列研究

背景癫痫和注意力缺陷/多动障碍(ADHD)密切相关。然而,导致它们同时发生的根本因素仍不清楚。共同的遗传责任已被提议作为一种可能的机制。因此,我们本研究的目标是调查癫痫和多动症的家族聚集性,并估计遗传和环境风险因素对其同时发生的影响。方法 我们通过瑞典国家登记册识别了 1,899,654 名出生于 1987 年至 2006 年之间的人,并将每个人与其亲生亲属联系起来。我们使用逻辑回归来估计个体和亲属之间癫痫和 ADHD 之间的关联。使用定量遗传模型将跨疾病协方差分解为遗传和环境因素。结果 癫痫患者患 ADHD 的风险显着增加(优势比 [OR] = 3.47,95% 置信区间 [CI] = 3.33-3.62)。这种风险增加延伸至母亲患有癫痫的儿童(OR = 1.85,95% CI = 1.75-1.96)、父亲患有癫痫的儿童(OR = 1.64,95% CI = 1.54-1.74)、全兄弟姐妹(OR = 1.56, 95% CI = 1.46-1.67)、同父异母兄弟姐妹 (OR = 1.28, 95% CI = 1.14-1.43)、同父异母兄弟姐妹 (OR = 1.10, 95% CI = 0.96-1.25) 和表兄弟姐妹 (OR = 1.15, 95% CI = 1.10-1.20)。遗传相关性为 0.21(95% CI = 0.02-0.40),解释了癫痫和 ADHD 之间 40% 的表型相关性,其余方差主要由非共享环境因素解释(49%,非共享环境相关性 = 0.36,95% CI = 0.23-0.49)。共享环境因素对跨疾病重叠的贡献不具有统计显着性(11%,共享环境相关性 = 0.32,95% CI = -0.16-0.79)。结论 这项研究表明,癫痫和 ADHD 之间存在着密切且病因复杂的关联,共同的家族因素和个体特有的危险因素导致这些疾病同时发生。我们的研究结果表明,与其他神经发育障碍相比,癫痫和多动症的遗传风险可能较低。
更新日期:2018-01-01
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