eprintid: 1536203
rev_number: 39
eprint_status: archive
userid: 608
dir: disk0/01/53/62/03
datestamp: 2017-01-19 14:54:25
lastmod: 2021-09-20 00:08:51
status_changed: 2017-02-27 14:44:38
type: article
metadata_visibility: show
creators_name: Direk, N
creators_name: Williams, S
creators_name: Smith, JA
creators_name: Ripke, S
creators_name: Air, T
creators_name: Amare, AT
creators_name: Amin, N
creators_name: Baune, BT
creators_name: Bennett, DA
creators_name: Blackwood, DH
creators_name: Boomsma, D
creators_name: Breen, G
creators_name: Buttenschøn, HN
creators_name: Byrne, EM
creators_name: Børglum, AD
creators_name: Castelao, E
creators_name: Cichon, S
creators_name: Clarke, TK
creators_name: Cornelis, MC
creators_name: Dannlowski, U
creators_name: De Jager, PL
creators_name: Demirkan, A
creators_name: Domenici, E
creators_name: van Duijn, CM
creators_name: Dunn, EC
creators_name: Eriksson, JG
creators_name: Esko, T
creators_name: Faul, JD
creators_name: Ferrucci, L
creators_name: Fornage, M
creators_name: de Geus, E
creators_name: Gill, M
creators_name: Gordon, SD
creators_name: Grabe, HJ
creators_name: van Grootheest, G
creators_name: Hamilton, SP
creators_name: Hartman, CA
creators_name: Heath, AC
creators_name: Hek, K
creators_name: Hofman, A
creators_name: Homuth, G
creators_name: Horn, C
creators_name: Jan Hottenga, J
creators_name: Kardia, SL
creators_name: Kloiber, S
creators_name: Koenen, K
creators_name: Kutalik, Z
creators_name: Ladwig, KH
creators_name: Lahti, J
creators_name: Levinson, DF
creators_name: Lewis, CM
creators_name: Lewis, G
creators_name: Li, QS
creators_name: Llewellyn, DJ
creators_name: Lucae, S
creators_name: Lunetta, KL
creators_name: MacIntyre, DJ
creators_name: Madden, P
creators_name: Martin, NG
creators_name: McIntosh, AM
creators_name: Metspalu, A
creators_name: Milaneschi, Y
creators_name: Montgomery, GW
creators_name: Mors, O
creators_name: Mosley, TH
creators_name: Murabito, JM
creators_name: Müller-Myhsok, B
creators_name: Nöthen, MM
creators_name: Nyholt, DR
creators_name: O'Donovan, MC
creators_name: Penninx, BW
creators_name: Pergadia, ML
creators_name: Perlis, R
creators_name: Potash, JB
creators_name: Preisig, M
creators_name: Purcell, SM
creators_name: Quiroz, JA
creators_name: Räikkönen, K
creators_name: Rice, JP
creators_name: Rietschel, M
creators_name: Rivera, M
creators_name: Schulze, TG
creators_name: Shi, J
creators_name: Shyn, S
creators_name: Sinnamon, GC
creators_name: Smit, JH
creators_name: Smoller, JW
creators_name: Snieder, H
creators_name: Tanaka, T
creators_name: Tansey, KE
creators_name: Teumer, A
creators_name: Uher, R
creators_name: Umbricht, D
creators_name: Van der Auwera, S
creators_name: Ware, EB
creators_name: Weir, DR
creators_name: Weissman, MM
creators_name: Willemsen, G
creators_name: Yang, J
creators_name: Zhao, W
creators_name: Tiemeier, H
creators_name: Sullivan, PF
title: An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D79
keywords: CHARGE consortium, Depressive symptoms, FHIT gene, Genome-wide association study, Major depressive disorder, Psychiatric Genomics Consortium
note: © 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.
abstract: 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.
date: 2017-09
date_type: published
official_url: http://doi.org/10.1016/j.biopsych.2016.11.013
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
article_type_text: Journal Article
verified: verified_manual
elements_id: 1200868
doi: 10.1016/j.biopsych.2016.11.013
pii: S0006-3223(16)33068-2
lyricists_name: Lewis, Glyn
lyricists_id: GHLEW69
actors_name: Lewis, Glyn
actors_id: GHLEW69
actors_role: owner
full_text_status: public
publication: Biological Psychiatry
volume: 82
number: 5
pagerange: 322-329
event_location: United States
issn: 1873-2402
citation:        Direk, N;    Williams, S;    Smith, JA;    Ripke, S;    Air, T;    Amare, AT;    Amin, N;                                                                                                                                                                                                                                                                                                                                                                                             ... Sullivan, PF; + view all <#>        Direk, N;  Williams, S;  Smith, JA;  Ripke, S;  Air, T;  Amare, AT;  Amin, N;  Baune, BT;  Bennett, DA;  Blackwood, DH;  Boomsma, D;  Breen, G;  Buttenschøn, HN;  Byrne, EM;  Børglum, AD;  Castelao, E;  Cichon, S;  Clarke, TK;  Cornelis, MC;  Dannlowski, U;  De Jager, PL;  Demirkan, A;  Domenici, E;  van Duijn, CM;  Dunn, EC;  Eriksson, JG;  Esko, T;  Faul, JD;  Ferrucci, L;  Fornage, M;  de Geus, E;  Gill, M;  Gordon, SD;  Grabe, HJ;  van Grootheest, G;  Hamilton, SP;  Hartman, CA;  Heath, AC;  Hek, K;  Hofman, A;  Homuth, G;  Horn, C;  Jan Hottenga, J;  Kardia, SL;  Kloiber, S;  Koenen, K;  Kutalik, Z;  Ladwig, KH;  Lahti, J;  Levinson, DF;  Lewis, CM;  Lewis, G;  Li, QS;  Llewellyn, DJ;  Lucae, S;  Lunetta, KL;  MacIntyre, DJ;  Madden, P;  Martin, NG;  McIntosh, AM;  Metspalu, A;  Milaneschi, Y;  Montgomery, GW;  Mors, O;  Mosley, TH;  Murabito, JM;  Müller-Myhsok, B;  Nöthen, MM;  Nyholt, DR;  O'Donovan, MC;  Penninx, BW;  Pergadia, ML;  Perlis, R;  Potash, JB;  Preisig, M;  Purcell, SM;  Quiroz, JA;  Räikkönen, K;  Rice, JP;  Rietschel, M;  Rivera, M;  Schulze, TG;  Shi, J;  Shyn, S;  Sinnamon, GC;  Smit, JH;  Smoller, JW;  Snieder, H;  Tanaka, T;  Tansey, KE;  Teumer, A;  Uher, R;  Umbricht, D;  Van der Auwera, S;  Ware, EB;  Weir, DR;  Weissman, MM;  Willemsen, G;  Yang, J;  Zhao, W;  Tiemeier, H;  Sullivan, PF;   - view fewer <#>    (2017)    An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.                   Biological Psychiatry , 82  (5)   pp. 322-329.    10.1016/j.biopsych.2016.11.013 <https://doi.org/10.1016/j.biopsych.2016.11.013>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1536203/1/Lewis_Direk%202017.pdf