RT Journal Article
T1 An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.
A1 Direk, Nese
A1 Williams, Stephanie
A1 Smith, Jennifer A
A1 Ripke, Stephan
A1 Air, Tracy
A1 Amare, Azmeraw T
A1 Amin, Najaf
A1 Baune, Bernhard T
A1 Bennett, David A
A1 Blackwood, Douglas H R
A1 Boomsma, Dorret
A1 Breen, Gerome
A1 Buttenschøn, Henriette N
A1 Byrne, Enda M
A1 Børglum, Anders D
A1 Castelao, Enrique
A1 Cichon, Sven
A1 Clarke, Toni-Kim
A1 Cornelis, Marilyn C
A1 Dannlowski, Udo
A1 De Jager, Philip L
A1 Demirkan, Ayse
A1 Domenici, Enrico
A1 van Duijn, Cornelia M
A1 Dunn, Erin C
A1 Eriksson, Johan G
A1 Esko, Tonu
A1 Faul, Jessica D
A1 Ferrucci, Luigi
A1 Fornage, Myriam
A1 de Geus, Eco
A1 Gill, Michael
A1 Gordon, Scott D
A1 Grabe, Hans Jörgen
A1 van Grootheest, Gerard
A1 Hamilton, Steven P
A1 Hartman, Catharina A
A1 Heath, Andrew C
A1 Hek, Karin
A1 Hofman, Albert
A1 Homuth, Georg
A1 Horn, Carsten
A1 Jan Hottenga, Jouke
A1 Kardia, Sharon L R
A1 Kloiber, Stefan
A1 Koenen, Karestan
A1 Kutalik, Zoltán
A1 Ladwig, Karl-Heinz
A1 Lahti, Jari
A1 Levinson, Douglas F
A1 Lewis, Cathryn M
A1 Lewis, Glyn
A1 Li, Qingqin S
A1 Llewellyn, David J
A1 Lucae, Susanne
A1 Lunetta, Kathryn L
A1 MacIntyre, Donald J
A1 Madden, Pamela
A1 Martin, Nicholas G
A1 McIntosh, Andrew M
A1 Metspalu, Andres
A1 Milaneschi, Yuri
A1 Montgomery, Grant W
A1 Mors, Ole
A1 Mosley, Thomas H
A1 Murabito, Joanne M
A1 Müller-Myhsok, Bertram
A1 Nöthen, Markus M
A1 Nyholt, Dale R
A1 O'Donovan, Michael C
A1 Penninx, Brenda W
A1 Pergadia, Michele L
A1 Perlis, Roy
A1 Potash, James B
A1 Preisig, Martin
A1 Purcell, Shaun M
A1 Quiroz, Jorge A
A1 Räikkönen, Katri
A1 Rice, John P
A1 Rietschel, Marcella
A1 Rivera, Margarita
A1 Schulze, Thomas G
A1 Shi, Jianxin
A1 Shyn, Stanley
A1 Sinnamon, Grant C
A1 Smit, Johannes H
A1 Smoller, Jordan W
A1 Snieder, Harold
A1 Tanaka, Toshiko
A1 Tansey, Katherine E
A1 Teumer, Alexander
A1 Uher, Rudolf
A1 Umbricht, Daniel
A1 Van der Auwera, Sandra
A1 Ware, Erin B
A1 Weir, David R
A1 Weissman, Myrna M
A1 Willemsen, Gonneke
A1 Yang, Jingyun
A1 Zhao, Wei
A1 Tiemeier, Henning
A1 Sullivan, Patrick F
K1 CHARGE consortium
K1 Depressive symptoms
K1 FHIT gene
K1 Genome-wide association study
K1 Major depressive disorder
K1 Psychiatric Genomics Consortium
AB The genetics of depression has been explored in genome-wide association studies that focused on either major depressive disorder or depressive symptoms with mostly negative findings. A broad depression phenotype including both phenotypes has not been tested previously using a genome-wide association approach. We aimed to identify genetic polymorphisms significantly associated with a broad phenotype from depressive symptoms to major depressive disorder. We analyzed two prior studies of 70,017 participants of European ancestry from general and clinical populations in the discovery stage. We performed a replication meta-analysis of 28,328 participants. Single nucleotide polymorphism (SNP)-based heritability and genetic correlations were calculated using linkage disequilibrium score regression. Discovery and replication analyses were performed using a p-value-based meta-analysis. Lifetime major depressive disorder and depressive symptom scores were used as the outcome measures. The SNP-based heritability of major depressive disorder was 0.21 (SE = 0.02), the SNP-based heritability of depressive symptoms was 0.04 (SE = 0.01), and their genetic correlation was 1.001 (SE = 0.2). We found one genome-wide significant locus related to the broad depression phenotype (rs9825823, chromosome 3: 61,082,153, p = 8.2 × 10-9) located in an intron of the FHIT gene. We replicated this SNP in independent samples (p = .02) and the overall meta-analysis of the discovery and replication cohorts (1.0 × 10-9). This large study identified a new locus for depression. Our results support a continuum between depressive symptoms and major depressive disorder. A phenotypically more inclusive approach may help to achieve the large sample sizes needed to detect susceptibility loci for depression.
PB Elsevier Inc.
YR 2016
FD 2016-12-08
LK http://hdl.handle.net/10668/10736
UL http://hdl.handle.net/10668/10736
LA en
NO Direk N, Williams S, Smith JA, Ripke S, Air T, Amare AT, et al. An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype. Biol Psychiatry. 2017 Sep 1;82(5):322-329.
DS RISalud
RD Apr 7, 2025