TY - JOUR
T1 - Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression
AU - Hagenaars, Saskia P.
AU - Coleman, Jonathan R.I.
AU - Choi, Shing Wan
AU - Gaspar, Héléna
AU - Adams, Mark J.
AU - Howard, David M.
AU - Hodgson, Karen
AU - Traylor, Matthew
AU - Air, Tracy M.
AU - Andlauer, Till F.M.
AU - Arolt, Volker
AU - Baune, Bernhard T.
AU - Binder, Elisabeth B.
AU - Blackwood, Douglas H.R.
AU - Boomsma, Dorret I.
AU - Campbell, Archie
AU - Cearns, Micah
AU - Czamara, Darina
AU - Dannlowski, Udo
AU - Domschke, Katharina
AU - de Geus, Eco J.C.
AU - Hamilton, Steven P.
AU - Hayward, Caroline
AU - Hickie, Ian B.
AU - Hottenga, Jouke Jan
AU - Ising, Marcus
AU - Jones, Ian
AU - Jones, Lisa
AU - Kutalik, Zoltan
AU - Lucae, Susanne
AU - Martin, Nicholas G.
AU - Milaneschi, Yuri
AU - Mueller-Myhsok, Bertram
AU - Owen, Michael J.
AU - Padmanabhan, Sandosh
AU - Penninx, Brenda W.J.H.
AU - Pistis, Giorgio
AU - Porteous, David J.
AU - Preisig, Martin
AU - Ripke, Stephan
AU - Shyn, Stanley I.
AU - Sullivan, Patrick F.
AU - Whitfield, John B.
AU - Wray, Naomi R.
AU - McIntosh, Andrew M.
AU - Deary, Ian J.
AU - Breen, Gerome
AU - Lewis, Cathryn M.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
KW - age at onset
KW - cardio-metabolic disease
KW - depression
KW - genetics
KW - polygenic risk scores
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U2 - 10.1002/ajmg.b.32807
DO - 10.1002/ajmg.b.32807
M3 - Article
C2 - 32681593
SN - 1552-4841
VL - 183
SP - 309
EP - 330
JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
IS - 6
ER -
