Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes

Mei-Hsin Su; Ying-Hsiu Shih; Yen-Feng Lin; Pei-Chun Chen; Chia-Yen Chen; Po-Chang Hsiao; Yi-Jiun Pan; Yu-Li Liu; Shih-Jen Tsai; Po-Hsiu Kuo; Chi-Shin Wu; Yen-Tsung Huang; Shi-Heng Wang

doi:10.1007/s00125-022-05665-x

Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes

Diabetologia. 2022 May;65(5):800-810. doi: 10.1007/s00125-022-05665-x. Epub 2022 Feb 23.

Authors

Mei-Hsin Su¹, Ying-Hsiu Shih², Yen-Feng Lin³, Pei-Chun Chen², Chia-Yen Chen^{4

5}, Po-Chang Hsiao⁶, Yi-Jiun Pan⁷, Yu-Li Liu³, Shih-Jen Tsai⁸, Po-Hsiu Kuo⁶, Chi-Shin Wu⁹, Yen-Tsung Huang¹⁰, Shi-Heng Wang^{11

12}

Affiliations

¹ Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan.
² Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan.
³ Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli, Taiwan.
⁴ Biogen, Cambridge, MA, USA.
⁵ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ College of Public Health, National Taiwan University, Taipei, Taiwan.
⁷ School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan.
⁸ Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
⁹ Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
¹⁰ Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
¹¹ Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, Taiwan. wangsh@mail.cmu.edu.tw.
¹² Department of Public Health, College of Public Health, China Medical University, Taichung, Taiwan. wangsh@mail.cmu.edu.tw.

PMID: 35195735
DOI: 10.1007/s00125-022-05665-x

Abstract

Aims/hypothesis: Psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD), are highly comorbid with type 2 diabetes. However, the mechanisms underlying such comorbidity are understudied. This study explored the familial aggregation of common psychiatric disorders and type 2 diabetes by testing family history association, and investigated the shared genetic loading between them by testing the polygenic risk score (PRS) association.

Methods: A total of 105,184 participants were recruited from the Taiwan Biobank, and genome-wide genotyping data were available for 95,238 participants. The Psychiatric Genomics Consortium-derived PRS for SCZ, MDD and BPD was calculated. Logistic regression was used to estimate the OR with CIs between a family history of SCZ/MDD/BPD and a family history of type 2 diabetes, and between the PRS and the risk of type 2 diabetes.

Results: A family history of type 2 diabetes was associated with a family history of SCZ (OR 1.23, 95% CI 1.08, 1.40), MDD (OR 1.19, 95% CI 1.13, 1.26) and BPD (OR 1.26, 95% CI 1.15, 1.39). Compared with paternal type 2 diabetes, maternal type 2 diabetes was associated with a higher risk of a family history of SCZ. SCZ PRS was negatively associated with type 2 diabetes in women (OR 0.92, 95% CI 0.88, 0.97), but not in men; the effect of SCZ PRS reduced after adjusting for BMI. MDD PRS was positively associated with type 2 diabetes (OR 1.04, 95% CI 1.00, 1.07); the effect of MDD PRS reduced after adjusting for BMI or smoking. BPD PRS was not associated with type 2 diabetes.

Conclusions/interpretation: The comorbidity of type 2 diabetes with psychiatric disorders may be explained by shared familial factors. The shared polygenic loading between MDD and type 2 diabetes implies not only pleiotropy but also a shared genetic aetiology for the mechanism behind the comorbidity. The negative correlation between polygenic loading for SCZ and type 2 diabetes implies the role of environmental factors.

Keywords: Bipolar disorder; Comorbidity; Depression; Diabetes; Familial aggregation; Polygenic risk score; Schizophrenia.

MeSH terms

Depressive Disorder, Major* / genetics
Diabetes Mellitus, Type 2* / genetics
Female
Genetic Predisposition to Disease / genetics
Genome-Wide Association Study
Humans
Male
Mental Disorders*