Distinct biological signature and modifiable risk factors underlie the comorbidity between major depressive disorder and cardiovascular disease

被引：13

作者：

Bergstedt, Jacob ^{[1
]}

Pasman, Joelle A. ^{[2
]}

Ma, Ziyan ^{[2
]}

Harder, Arvid ^{[2
]}

Yao, Shuyang ^{[2
,3
]}

Parker, Nadine ^{[4
,5
]}

Treur, Jorien L. ^{[6
]}

Smit, Dirk J. A. ^{[6
]}

Frei, Oleksandr ^{[4
,5
,7
]}

Shadrin, Alexey A. ^{[4
,5
,8
]}

Meijsen, Joeri J. ^{[9
]}

Shen, Qing ^{[1
,10
,11
]}

Hagg, Sara ^{[2
]}

Tornvall, Per ^{[12
]}

Buil, Alfonso ^{[9
]}

Werge, Thomas ^{[9
,13
]}

Hjerling-Leffler, Jens ^{[3
]}

Als, Thomas D. ^{[14
,15
,16
]}

Borglum, Anders D. ^{[15
,16
]}

Lewis, Cathryn M. ^{[17
,18
]}

Mcintosh, Andrew M. ^{[19
,20
]}

Valdimarsdottir, Unnur A. ^{[1
,21
,22
]}

Andreassen, Ole A. ^{[4
,5
,8
]}

Sullivan, Patrick F. ^{[2
,23
,24
]}

Lu, Yi ^{[2
]}

Fang, Fang ^{[1
]}

机构：

[1] Karolinska Inst, Inst Environm Med, Unit Integrat Epidemiol, Stockholm, Sweden

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

[3] Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden

[4] Univ Oslo, Ctr Precis Psychiat, Div Mental Hlth & Addict, Oslo, Norway

[5] Oslo Univ Hosp, Oslo, Norway

[6] Univ Amsterdam, Dept Psychiat, Genet Epidemiol, Amsterdam UMC, Amsterdam, Netherlands

[7] Univ Oslo, Ctr Bioinformat, Dept Informat, Oslo, Norway

[8] Univ Oslo, KG Jebsen Ctr Neurodev Disorders, Oslo, Norway

[9] Mental Hlth Ctr Sct Hans, Inst Biol Psychiat, Mental Hlth Serv Copenhagen, Roskilde, Denmark

[10] Tongji Univ, Sch Med, Clin Res Ctr Mental Disorders, Shanghai Pudong New Area Mental Hlth Ctr, Shanghai, Peoples R China

[11] Tongji Univ, Inst Adv Study, Shanghai, Peoples R China

[12] Karolinska Inst, Dept Clin Sci & Educ, Sodersjukhuset, Stockholm, Sweden

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

[14] Aarhus Univ Hosp, Dept Mol Med MOMA, Mol Diagnost Lab, Aarhus, Denmark

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

[16] Ctr Genom & Personalized Med, Aarhus, Denmark

[17] Kings Coll London, Social Genet & Dev Psychiat Ctr, London, England

[18] Kings Coll London, Dept Med & Mol Genet, London, England

[19] Univ Edinburgh, Royal Edinburgh Hosp, Ctr Clin Brain Sci, Edinburgh, Scotland

[20] Univ Edinburgh, Ctr Genom & Expt Med, Edinburgh, Scotland

[21] Univ Iceland, Fac Med, Ctr Publ Hlth Sci, Sch Hlth Sci, Reykjavik, Iceland

[22] Harvard Univ, Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[23] Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA

[24] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

来源：

NATURE CARDIOVASCULAR RESEARCH | 2024年 / 3卷 / 06期

基金：

欧盟地平线“2020”; 欧洲研究理事会; 瑞典研究理事会; 英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; LD SCORE REGRESSION; INFLAMMATION; PATHOPHYSIOLOGY; HERITABILITY; INSTRUMENTS; CHILDHOOD; OUTCOMES; HEALTH;

D O I：

10.1038/s44161-024-00488-y

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Major depressive disorder (MDD) and cardiovascular disease (CVD) are often comorbid, resulting in excess morbidity and mortality. Here we show that CVDs share most of their genetic risk factors with MDD. Multivariate genome-wide association analysis of shared genetic liability between MDD and atherosclerotic CVD revealed seven loci and distinct patterns of tissue and brain cell-type enrichments, suggesting the involvement of the thalamus. Part of the genetic overlap was explained by shared inflammatory, metabolic and psychosocial or lifestyle risk factors. Our data indicated causal effects of genetic liability to MDD on CVD risk, but not from most CVDs to MDD, and showed that the causal effects were partly explained by metabolic and psychosocial or lifestyle factors. The distinct signature of MDD-atherosclerotic CVD comorbidity suggests an immunometabolic subtype of MDD that is more strongly associated with CVD than overall MDD. In summary, we identified biological mechanisms underlying MDD-CVD comorbidity and modifiable risk factors for prevention of CVD in individuals with MDD. Bergstedt et al. show that the effects of genetic liability to major depressive disorder can cause an increase in cardiovascular risk and that metabolic, psychological and lifestyle factors are partly responsible for this association.

引用

页码：754 / 769

页数：34

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