TY - JOUR
T1 - Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank
AU - Coleman, Jonathan R. I.
AU - Peyrot, Wouter J.
AU - Purves, Kirstin
AU - Davis, Katrina A. S.
AU - Rayner, Christopher
AU - Choi, Shing Wan
AU - Huebel, Christopher
AU - Gaspar, Héléna A.
AU - Kan, Carol
AU - der Auwera, Sandra Van
AU - Adams, Mark J.
AU - Lyall, Donald
AU - Choi, Karmel W.
AU - Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium
AU - Dunn, Erin C.
AU - Vassos, Evangelos
AU - Danese, Andrea
AU - Maughan, Barbara
AU - Grabe, H. J.
AU - Lewis, Cathryn M.
AU - O'Reilly, Paul F.
AU - McIntosh, Andrew M.
AU - Smith, Daniel J
AU - Wray, Naomi R.
AU - Hotopf, Matthew
AU - Eley, Thalia
AU - Breen, Gerome
AU - Howard, David
PY - 2020/7/1
Y1 - 2020/7/1
N2 - Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8x10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3x10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.
AB - Depression is more frequent among individuals exposed to traumatic events. Both trauma exposure and depression are heritable. However, the relationship between these traits, including the role of genetic risk factors, is complex and poorly understood. When modelling trauma exposure as an environmental influence on depression, both gene-environment correlations and gene-environment interactions have been observed. The UK Biobank concurrently assessed Major Depressive Disorder (MDD) and self-reported lifetime exposure to traumatic events in 126,522 genotyped individuals of European ancestry. We contrasted genetic influences on MDD stratified by reported trauma exposure (final sample size range: 24,094-92,957). The SNP-based heritability of MDD with reported trauma exposure (24%) was greater than MDD without reported trauma exposure (12%). Simulations showed that this is not confounded by the strong, positive genetic correlation observed between MDD and reported trauma exposure. We also observed that the genetic correlation between MDD and waist circumference was only significant in individuals reporting trauma exposure (rg = 0.24, p = 1.8x10-7 versus rg = -0.05, p = 0.39 in individuals not reporting trauma exposure, difference p = 2.3x10-4). Our results suggest that the genetic contribution to MDD is greater when reported trauma is present, and that a complex relationship exists between reported trauma exposure, body composition, and MDD.
UR - http://www.scopus.com/inward/record.url?scp=85078355026&partnerID=8YFLogxK
U2 - 10.1038/s41380-019-0546-6
DO - 10.1038/s41380-019-0546-6
M3 - Article
SN - 1359-4184
VL - 25
SP - 1430
EP - 1446
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 7
ER -