Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank

Anna E. Fürtjes; Jonathan R.I. Coleman; Jess Tyrrell; Cathryn M. Lewis; Saskia P. Hagenaars

doi:10.1017/S0033291721000945

Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank

Anna E. Fürtjes^*, Jonathan R.I. Coleman, Jess Tyrrell, Cathryn M. Lewis, Saskia P. Hagenaars

^*Corresponding author for this work

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

7 Citations (Scopus)

Abstract

Background People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits. Methods In a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits. Results Several traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations. Conclusions This large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.

Original language	English
Journal	Psychological Medicine
DOIs	https://doi.org/10.1017/S0033291721000945
Publication status	Accepted/In press - 2021

Keywords

biomarkers
Bipolar disorder
cardiometabolic abnormalities
cardiovascular disease
genetic correlation
polygenic score

UN SDGs

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

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10.1017/S0033291721000945

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title = "Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank",

abstract = "Background People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits. Methods In a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits. Results Several traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations. Conclusions This large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.",

keywords = "biomarkers, Bipolar disorder, cardiometabolic abnormalities, cardiovascular disease, genetic correlation, polygenic score",

author = "F{\"u}rtjes, {Anna E.} and Coleman, {Jonathan R.I.} and Jess Tyrrell and Lewis, {Cathryn M.} and Hagenaars, {Saskia P.}",

year = "2021",

doi = "10.1017/S0033291721000945",

language = "English",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

}

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T1 - Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank

AU - Fürtjes, Anna E.

AU - Coleman, Jonathan R.I.

AU - Tyrrell, Jess

AU - Lewis, Cathryn M.

AU - Hagenaars, Saskia P.

PY - 2021

Y1 - 2021

N2 - Background People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits. Methods In a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits. Results Several traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations. Conclusions This large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.

AB - Background People with bipolar disorder (BPD) are more likely to die prematurely, which is partly attributed to comorbid cardiometabolic traits. Previous studies report cardiometabolic abnormalities in BPD, but their shared aetiology remains poorly understood. This study examined the phenotypic associations and shared genetic aetiology between BPD and various cardiometabolic traits. Methods In a subset of the UK Biobank sample (N = 61 508) we investigated phenotypic associations between BPD (ncases = 4186) and cardiometabolic traits, represented by biomarkers, anthropometric traits and cardiometabolic diseases. To determine shared genetic aetiology in European ancestry, polygenic risk scores (PRS) and genetic correlations were calculated between BPD and cardiometabolic traits. Results Several traits were significantly associated with increased risk for BPD, namely low total cholesterol, low high-density lipoprotein cholesterol, high triglycerides, high glycated haemoglobin, low systolic blood pressure, high body mass index, high waist-to-hip ratio; and stroke, coronary artery disease and type 2 diabetes diagnosis. BPD was associated with higher polygenic risk for triglycerides, waist-to-hip ratio, coronary artery disease and type 2 diabetes. Shared genetic aetiology persisted for coronary artery disease, when correcting PRS associations for cardiometabolic base phenotypes. Associations were not replicated using genetic correlations. Conclusions This large study identified increased phenotypic cardiometabolic abnormalities in BPD participants. It is found that the comorbidity of coronary artery disease may be based on shared genetic aetiology. These results motivate hypothesis-driven research to consider individual cardiometabolic traits rather than a composite metabolic syndrome when attempting to disentangle driving mechanisms of cardiometabolic abnormalities in BPD.

KW - biomarkers

KW - Bipolar disorder

KW - cardiometabolic abnormalities

KW - cardiovascular disease

KW - genetic correlation

KW - polygenic score

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U2 - 10.1017/S0033291721000945

DO - 10.1017/S0033291721000945

M3 - Article

AN - SCOPUS:85103312532

SN - 0033-2917

JO - Psychological Medicine

JF - Psychological Medicine

ER -

Associations and limited shared genetic aetiology between bipolar disorder and cardiometabolic traits in the UK Biobank

Abstract

Keywords

UN SDGs

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