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Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics ( IF 1.6 ) Pub Date : 2020-07-18 , DOI: 10.1002/ajmg.b.32807
Saskia P Hagenaars 1, 2 , Jonathan R I Coleman 1, 2 , Shing Wan Choi 1 , Héléna Gaspar 1, 2 , Mark J Adams 3 , David M Howard 1, 3 , Karen Hodgson 1, 2 , Matthew Traylor 4 , Tracy M Air 5 , Till F M Andlauer 6, 7 , Volker Arolt 8 , Bernhard T Baune 8, 9, 10 , Elisabeth B Binder 6, 11 , Douglas H R Blackwood 12 , Dorret I Boomsma 13 , Archie Campbell 12 , Micah Cearns 9 , Darina Czamara 6 , Udo Dannlowski 8 , Katharina Domschke 14, 15 , Eco J C de Geus 13 , Steven P Hamilton 16 , Caroline Hayward 12, 17 , Ian B Hickie 18 , Jouke Jan Hottenga 13 , Marcus Ising 19 , Ian Jones 20 , Lisa Jones 21 , Zoltan Kutalik 22, 23 , Susanne Lucae 19 , Nicholas G Martin 24 , Yuri Milaneschi 25 , Bertram Mueller-Myhsok 6, 26, 27 , Michael J Owen 20 , Sandosh Padmanabhan 12, 28 , Brenda W J H Penninx 25 , Giorgio Pistis 29 , David J Porteous 12 , Martin Preisig 29 , Stephan Ripke 30, 31, 32 , Stanley I Shyn 33 , Patrick F Sullivan 34, 35, 36 , John B Whitfield 24 , Naomi R Wray 37, 38 , Andrew M McIntosh 3, 12, 39 , Ian J Deary 39, 40 , Gerome Breen 1, 2 , Cathryn M Lewis 1, 2
Affiliation  

It is imperative to understand the specific and shared etiologies of major depression and cardio‐metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio‐metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio‐metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio‐metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.

中文翻译:


重度抑郁症和心脏代谢特征之间的遗传共病,按重度抑郁症发病年龄分层。



必须了解重度抑郁症和心脏代谢疾病的具体和共同病因,因为这两种特征经常共存,并且每种特征都对社会造成重大负担。这项研究探讨了重度抑郁症与心脏代谢特征之间是否存在遗传关联,以及这种关联是否按重度抑郁症发病年龄进行分层。进行多基因风险评分分析和连锁不平衡评分回归,以检查抑郁症病例控制状态( N例 = 40,940, N对照 = 67,532)、早期发病抑郁症( N = 15,844)和晚发抑郁症( N )之间是否存在共同遗传病因学差异。 = 15,800),包括来自精神病基因组学联盟、苏格兰一代和英国生物银行的 11 个数据集中的体重指数、冠状动脉疾病、中风和 2 型糖尿病。所有心脏代谢多基因风险评分均与抑郁状态相关。研究发现抑郁症与体重指数、冠状动脉疾病和 2 型糖尿病之间存在显着的遗传相关性。体重指数、冠状动脉疾病和 2 型糖尿病的较高多基因风险与早发和晚发抑郁症相关,而中风的较高多基因风险仅与晚发抑郁症相关。体重指数与晚发性抑郁症之间以及冠状动脉疾病与早发性和晚发性抑郁症之间发现了显着的遗传相关性。重度抑郁症和心脏代谢特征之间的表型关联可能部分反映了它们重叠的遗传病因学,无论抑郁症首次出现的年龄如何。
更新日期:2020-08-08
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