TY  - JOUR
KW  - CHARGE consortium
KW  -  Depressive symptoms
KW  -  FHIT gene
KW  -  Genome-wide association study
KW  -  Major depressive disorder
KW  -  Psychiatric Genomics Consortium
UR  - http://doi.org/10.1016/j.biopsych.2016.11.013
A1  - Direk, N
A1  - Williams, S
A1  - Smith, JA
A1  - Ripke, S
A1  - Air, T
A1  - Amare, AT
A1  - Amin, N
A1  - Baune, BT
A1  - Bennett, DA
A1  - Blackwood, DH
A1  - Boomsma, D
A1  - Breen, G
A1  - Buttenschøn, HN
A1  - Byrne, EM
A1  - Børglum, AD
A1  - Castelao, E
A1  - Cichon, S
A1  - Clarke, TK
A1  - Cornelis, MC
A1  - Dannlowski, U
A1  - De Jager, PL
A1  - Demirkan, A
A1  - Domenici, E
A1  - van Duijn, CM
A1  - Dunn, EC
A1  - Eriksson, JG
A1  - Esko, T
A1  - Faul, JD
A1  - Ferrucci, L
A1  - Fornage, M
A1  - de Geus, E
A1  - Gill, M
A1  - Gordon, SD
A1  - Grabe, HJ
A1  - van Grootheest, G
A1  - Hamilton, SP
A1  - Hartman, CA
A1  - Heath, AC
A1  - Hek, K
A1  - Hofman, A
A1  - Homuth, G
A1  - Horn, C
A1  - Jan Hottenga, J
A1  - Kardia, SL
A1  - Kloiber, S
A1  - Koenen, K
A1  - Kutalik, Z
A1  - Ladwig, KH
A1  - Lahti, J
A1  - Levinson, DF
A1  - Lewis, CM
A1  - Lewis, G
A1  - Li, QS
A1  - Llewellyn, DJ
A1  - Lucae, S
A1  - Lunetta, KL
A1  - MacIntyre, DJ
A1  - Madden, P
A1  - Martin, NG
A1  - McIntosh, AM
A1  - Metspalu, A
A1  - Milaneschi, Y
A1  - Montgomery, GW
A1  - Mors, O
A1  - Mosley, TH
A1  - Murabito, JM
A1  - Müller-Myhsok, B
A1  - Nöthen, MM
A1  - Nyholt, DR
A1  - O'Donovan, MC
A1  - Penninx, BW
A1  - Pergadia, ML
A1  - Perlis, R
A1  - Potash, JB
A1  - Preisig, M
A1  - Purcell, SM
A1  - Quiroz, JA
A1  - Räikkönen, K
A1  - Rice, JP
A1  - Rietschel, M
A1  - Rivera, M
A1  - Schulze, TG
A1  - Shi, J
A1  - Shyn, S
A1  - Sinnamon, GC
A1  - Smit, JH
A1  - Smoller, JW
A1  - Snieder, H
A1  - Tanaka, T
A1  - Tansey, KE
A1  - Teumer, A
A1  - Uher, R
A1  - Umbricht, D
A1  - Van der Auwera, S
A1  - Ware, EB
A1  - Weir, DR
A1  - Weissman, MM
A1  - Willemsen, G
A1  - Yang, J
A1  - Zhao, W
A1  - Tiemeier, H
A1  - Sullivan, PF
AV  - public
ID  - discovery1536203
SP  - 322
JF  - Biological Psychiatry
N2  - BACKGROUND: 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. METHODS: 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. RESULTS: 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)). CONCLUSIONS: 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.
VL  - 82
SN  - 1873-2402
EP  - 329
N1  - © Society of Biological Psychiatry, 2016. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at https://creativecommons.org/licenses/. Access may be initially restricted by the publisher.
Y1  - 2017/09//
TI  - An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
IS  - 5
ER  -