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

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^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

16 Scopus citations

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. Graphical abstract: [Figure not available: see fulltext.]

Original language	English
Pages (from-to)	800-810
Number of pages	11
Journal	Diabetologia
Volume	65
Issue number	5
DOIs	https://doi.org/10.1007/s00125-022-05665-x
State	Published - 05 2022
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Keywords

Bipolar disorder
Comorbidity
Depression
Diabetes
Familial aggregation
Polygenic risk score
Schizophrenia

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1007/s00125-022-05665-x

Cite this

@article{f95ade57461e4a70bce69f4e9b8b6afb,

title = "Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes",

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. Graphical abstract: [Figure not available: see fulltext.]",

keywords = "Bipolar disorder, Comorbidity, Depression, Diabetes, Familial aggregation, Polygenic risk score, Schizophrenia",

author = "Su, {Mei Hsin} and Shih, {Ying Hsiu} and Lin, {Yen Feng} and Chen, {Pei Chun} and Chen, {Chia Yen} and Hsiao, {Po Chang} and Pan, {Yi Jiun} and Liu, {Yu Li} and Tsai, {Shih Jen} and Kuo, {Po Hsiu} and Wu, {Chi Shin} and Huang, {Yen Tsung} and Wang, {Shi Heng}",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.",

year = "2022",

month = may,

doi = "10.1007/s00125-022-05665-x",

language = "英语",

volume = "65",

pages = "800--810",

journal = "Diabetologia",

issn = "0012-186X",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "5",

}

TY - JOUR

T1 - Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes

AU - Su, Mei Hsin

AU - Shih, Ying Hsiu

AU - Lin, Yen Feng

AU - Chen, Pei Chun

AU - Chen, Chia Yen

AU - Hsiao, Po Chang

AU - Pan, Yi Jiun

AU - Liu, Yu Li

AU - Tsai, Shih Jen

AU - Kuo, Po Hsiu

AU - Wu, Chi Shin

AU - Huang, Yen Tsung

AU - Wang, Shi Heng

PY - 2022/5

Y1 - 2022/5

N2 - 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. Graphical abstract: [Figure not available: see fulltext.]

AB - 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. Graphical abstract: [Figure not available: see fulltext.]

KW - Bipolar disorder

KW - Comorbidity

KW - Depression

KW - Diabetes

KW - Familial aggregation

KW - Polygenic risk score

KW - Schizophrenia

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U2 - 10.1007/s00125-022-05665-x

DO - 10.1007/s00125-022-05665-x

M3 - 文章

C2 - 35195735

AN - SCOPUS:85125061568

SN - 0012-186X

VL - 65

SP - 800

EP - 810

JO - Diabetologia

JF - Diabetologia

IS - 5

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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