Theresa Wimberley, Isabell Brikell, Aske Astrup, Janne T Larsen, Liselotte V Petersen, Clara Albiñana, Bjarni J Vilhjálmsson, Cynthia M Bulik, Zheng Chang, Giuseppe Fanelli, Janita Bralten, Nina R Mota, Jordi Salas-Salvadó, Fernando Fernandez-Aranda, Monica Bulló, Barbara Franke, Anders Børglum, Preben B Mortensen, Henriette T Horsdal, Søren Dalsgaard
{"title":"2 型糖尿病和精神障碍的共同家族风险：全国多代遗传学研究。","authors":"Theresa Wimberley, Isabell Brikell, Aske Astrup, Janne T Larsen, Liselotte V Petersen, Clara Albiñana, Bjarni J Vilhjálmsson, Cynthia M Bulik, Zheng Chang, Giuseppe Fanelli, Janita Bralten, Nina R Mota, Jordi Salas-Salvadó, Fernando Fernandez-Aranda, Monica Bulló, Barbara Franke, Anders Børglum, Preben B Mortensen, Henriette T Horsdal, Søren Dalsgaard","doi":"10.1017/S0033291724001053","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (<i>n</i> = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":20891,"journal":{"name":"Psychological Medicine","volume":null,"pages":null},"PeriodicalIF":5.9000,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study.\",\"authors\":\"Theresa Wimberley, Isabell Brikell, Aske Astrup, Janne T Larsen, Liselotte V Petersen, Clara Albiñana, Bjarni J Vilhjálmsson, Cynthia M Bulik, Zheng Chang, Giuseppe Fanelli, Janita Bralten, Nina R Mota, Jordi Salas-Salvadó, Fernando Fernandez-Aranda, Monica Bulló, Barbara Franke, Anders Børglum, Preben B Mortensen, Henriette T Horsdal, Søren Dalsgaard\",\"doi\":\"10.1017/S0033291724001053\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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 (<i>n</i> = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":20891,\"journal\":{\"name\":\"Psychological Medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.9000,\"publicationDate\":\"2024-05-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychological Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1017/S0033291724001053\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PSYCHIATRY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychological Medicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1017/S0033291724001053","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}
Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study.
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.
期刊介绍：
Now in its fifth decade of publication, Psychological Medicine is a leading international journal in the fields of psychiatry, related aspects of psychology and basic sciences. From 2014, there are 16 issues a year, each featuring original articles reporting key research being undertaken worldwide, together with shorter editorials by distinguished scholars and an important book review section. The journal''s success is clearly demonstrated by a consistently high impact factor.
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