Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: a nationwide multigenerational genetics study

被引：4

作者：

Wimberley, Theresa ^{[1
,2
,3
]}

Brikell, Isabell ^{[1
,4
,5
,6
]}

Astrup, Aske ^{[1
]}

Larsen, Janne T. ^{[1
,2
]}

Petersen, Liselotte V. ^{[1
,2
]}

Albinana, Clara ^{[1
]}

Vilhjalmsson, Bjarni J. ^{[1
,7
]}

Bulik, Cynthia M. ^{[5
,8
,9
]}

Chang, Zheng ^{[5
]}

Fanelli, Giuseppe ^{[10
,11
,12
]}

Bralten, Janita ^{[10
,11
]}

Mota, Nina R. ^{[10
,11
]}

Salas-Salvado, Jordi ^{[13
,14
,15
]}

Fernandez-Aranda, Fernando ^{[15
,16
,17
,18
]}

Bullo, Monica ^{[13
,14
,15
,19
]}

Franke, Barbara ^{[10
,11
,20
]}

Borglum, Anders ^{[2
,6
]}

Mortensen, Preben B. ^{[1
,2
,3
]}

Horsdal, Henriette T. ^{[1
]}

Dalsgaard, Soren ^{[1
,2
,21
,22
]}

机构：

[1] Aarhus Univ, Natl Ctr Register Based Res, Sch Business & Social Sci, Aarhus, Denmark

[2] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark

[3] Aarhus Univ, Ctr Integrated Register Based Res CIRRAU, Aarhus, Denmark

[4] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway

[5] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden

[6] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[7] Aarhus Univ, Bioinformat Res Ctr, Aarhus, Denmark

[8] Univ North Carolina Chapel Hill, Chapel Hill, NC USA

[9] Univ North Carolina Chapel Hill, Dept Psychiat, Chapel Hill, NC USA

[10] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, Nijmegen, Netherlands

[11] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Nijmegen, Netherlands

[12] Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy

[13] Rovira & Virgili Univ Reus, Sch Med, Dept Biochem & Biotechnol, IISPV, Reus, Spain

[14] Inst Hlth Pere Virgili IISPV, Reus, Spain

[15] Inst Salud Carlos III ISCIII, Consorcio CIBER, MP Fisiopatol Obes & Nutr CIBERObn, Madrid, Spain

[16] Univ Hosp Bellvitge, Clin Psychol Unit, Lhospitalet De Llobregat, Spain

[17] Univ Barcelona, Sch Med & Hlth Sci, Dept Clin Sci, Lhospitalet De Llobregat, Spain

[18] Bellvitge Biomed Res Inst IDIBELL, Psychoneurobiol Eating & Addict Behav Grp, Lhospitalet De Llobregat, Spain

[19] Rovira & Virgili Univ, Ctr Environm Food & Toxicol Technol TecnATox, Reus 43201, Spain

[20] Radboud Univ Nijmegen, Med Ctr, Dept Cognit Neurosci, Nijmegen, Netherlands

[21] Copenhagen Univ Hosp, Child & Adolescent Mental Hlth Ctr, Mental Hlth Serv CPH, Copenhagen, Denmark

[22] Univ Copenhagen, Dept Clin Med Hlth & Med Sci, Copenhagen, Denmark

来源：

PSYCHOLOGICAL MEDICINE | 2024年 / 54卷 / 11期

关键词：

familial co-aggregation; genetic overlap; insulin resistance; non-insulin-dependent diabetes mellitus; polygenic risk; AGGREGATION;

D O I：

10.1017/S0033291724001053

中图分类号：

B849 [应用心理学];

学科分类号：

040203 ;

摘要：

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.

引用

页码：2976 / 2985

页数：10

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