Abstract：
BACKGROUND: Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM.
METHODS: We linked 659 906 individuals born in Denmark 1990-2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981-2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.
RESULTS: Among 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35-1.42; grandparents: 1.14, 1.13-1.15; and aunts/uncles: 1.19, 1.16-1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08-1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa.
CONCLUSIONS: Our findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.
METHODS: We linked 659 906 individuals born in Denmark 1990-2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981-2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.
RESULTS: Among 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35-1.42; grandparents: 1.14, 1.13-1.15; and aunts/uncles: 1.19, 1.16-1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08-1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa.
CONCLUSIONS: Our findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.
摘要：
背景：精神疾病和2型糖尿病（T2DM）是遗传性的，多基因，通常是合并症，然而，缺乏关于他们潜在的共同家庭风险的知识。我们使用家庭设计和T2DM多基因风险评分（T2DM-PRS）来研究精神疾病和T2DM之间的遗传关联。
方法：我们将1990-2000年在丹麦出生的659906人与父母联系起来，祖父母,和阿姨/叔叔使用基于人口的登记册。我们比较了患有或未诊断为11种特定精神疾病中的任何一种的儿童亲属中T2DM的发生率。包括神经精神和神经发育障碍，使用Cox回归。在1981-2008年出生的个体的基因分型样本（iPSYCH2015）中（n=134403），我们使用逻辑回归估计T2DM-PRS与这些精神疾病之间的关联.
结果：在5235300对亲戚中，患有精神疾病的个体的亲属患T2DM的风险增加,与近亲属的关联更强(父母:风险比=1.38,95%置信区间1.35-1.42;祖父母:1.14,1.13-1.15;阿姨/叔叔:1.19,1.16-1.22).在遗传样本中，T2DM-PRS的1个标准差增加与任何精神疾病的风险增加相关(比值比=1.11,1.08~1.14).家族性T2DM和T2DM-PRS与11种精神疾病中的7种显著相关。注意力缺陷/多动障碍和品行障碍最为强烈，与神经性厌食症相反。
结论：我们的发现与精神疾病相关的家族性共同聚集和更高的T2DM多基因倾向指向共有的家族性风险。这表明，部分合并症可以通过共同的家族风险来解释。潜在的机制仍然很大程度上未知，遗传和环境的贡献需要进一步研究。
方法：我们将1990-2000年在丹麦出生的659906人与父母联系起来，祖父母,和阿姨/叔叔使用基于人口的登记册。我们比较了患有或未诊断为11种特定精神疾病中的任何一种的儿童亲属中T2DM的发生率。包括神经精神和神经发育障碍，使用Cox回归。在1981-2008年出生的个体的基因分型样本（iPSYCH2015）中（n=134403），我们使用逻辑回归估计T2DM-PRS与这些精神疾病之间的关联.
结果：在5235300对亲戚中，患有精神疾病的个体的亲属患T2DM的风险增加,与近亲属的关联更强(父母:风险比=1.38,95%置信区间1.35-1.42;祖父母:1.14,1.13-1.15;阿姨/叔叔:1.19,1.16-1.22).在遗传样本中，T2DM-PRS的1个标准差增加与任何精神疾病的风险增加相关(比值比=1.11,1.08~1.14).家族性T2DM和T2DM-PRS与11种精神疾病中的7种显著相关。注意力缺陷/多动障碍和品行障碍最为强烈，与神经性厌食症相反。
结论：我们的发现与精神疾病相关的家族性共同聚集和更高的T2DM多基因倾向指向共有的家族性风险。这表明，部分合并症可以通过共同的家族风险来解释。潜在的机制仍然很大程度上未知，遗传和环境的贡献需要进一步研究。
