Shared familial risk for type 2 diabetes mellitus and psychiatric disorders: A nationwide multigenerational genetics study
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Shared familial risk for type 2 diabetes mellitus and psychiatric disorders : A nationwide multigenerational genetics study. / Wimberley, Theresa; Brikell, Isabell; Astrup, Aske; Larsen, Janne T.; Petersen, Liselotte V.; Albiñana, Clara; Vilhjálmsson, Bjarni J.; Bulik, Cynthia M.; Chang, Zheng; Fanelli, Giuseppe; Bralten, Janita; Mota, Nina R.; Salas-Salvadó, Jordi; Fernandez-Aranda, Fernando; Bulló, Monica; Franke, Barbara; Børglum, Anders; Mortensen, Preben B.; Horsdal, Henriette T.; Dalsgaard, Søren.
I: Psychological Medicine, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Shared familial risk for type 2 diabetes mellitus and psychiatric disorders
T2 - A nationwide multigenerational genetics study
AU - Wimberley, Theresa
AU - Brikell, Isabell
AU - Astrup, Aske
AU - Larsen, Janne T.
AU - Petersen, Liselotte V.
AU - Albiñana, Clara
AU - Vilhjálmsson, Bjarni J.
AU - Bulik, Cynthia M.
AU - Chang, Zheng
AU - Fanelli, Giuseppe
AU - Bralten, Janita
AU - Mota, Nina R.
AU - Salas-Salvadó, Jordi
AU - Fernandez-Aranda, Fernando
AU - Bulló, Monica
AU - Franke, Barbara
AU - Børglum, Anders
AU - Mortensen, Preben B.
AU - Horsdal, Henriette T.
AU - Dalsgaard, Søren
N1 - Publisher Copyright: Copyright © The Author(s), 2024. Published by Cambridge University Press.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - familial co-aggregation
KW - genetic overlap
KW - insulin resistance
KW - non-insulin-dependent diabetes mellitus
KW - polygenic risk
U2 - 10.1017/S0033291724001053
DO - 10.1017/S0033291724001053
M3 - Journal article
C2 - 38801094
AN - SCOPUS:85195067526
JO - Psychological Medicine
JF - Psychological Medicine
SN - 0033-2917
ER -
ID: 394532955