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An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.

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.

SUBMITTER: Direk N 

PROVIDER: S-EPMC5462867 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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An Analysis of Two Genome-wide Association Meta-analyses Identifies a New Locus for Broad Depression Phenotype.

Direk Nese N   Williams Stephanie S   Smith Jennifer A JA   Ripke Stephan S   Air Tracy T   Amare Azmeraw T AT   Amin Najaf N   Baune Bernhard T BT   Bennett David A DA   Blackwood Douglas H R DHR   Boomsma Dorret D   Breen Gerome G   Buttenschøn Henriette N HN   Byrne Enda M EM   Børglum Anders D AD   Castelao Enrique E   Cichon Sven S   Clarke Toni-Kim TK   Cornelis Marilyn C MC   Dannlowski Udo U   De Jager Philip L PL   Demirkan Ayse A   Domenici Enrico E   van Duijn Cornelia M CM   Dunn Erin C EC   Eriksson Johan G JG   Esko Tonu T   Faul Jessica D JD   Ferrucci Luigi L   Fornage Myriam M   de Geus Eco E   Gill Michael M   Gordon Scott D SD   Grabe Hans Jörgen HJ   van Grootheest Gerard G   Hamilton Steven P SP   Hartman Catharina A CA   Heath Andrew C AC   Hek Karin K   Hofman Albert A   Homuth Georg G   Horn Carsten C   Jan Hottenga Jouke J   Kardia Sharon L R SLR   Kloiber Stefan S   Koenen Karestan K   Kutalik Zoltán Z   Ladwig Karl-Heinz KH   Lahti Jari J   Levinson Douglas F DF   Lewis Cathryn M CM   Lewis Glyn G   Li Qingqin S QS   Llewellyn David J DJ   Lucae Susanne S   Lunetta Kathryn L KL   MacIntyre Donald J DJ   Madden Pamela P   Martin Nicholas G NG   McIntosh Andrew M AM   Metspalu Andres A   Milaneschi Yuri Y   Montgomery Grant W GW   Mors Ole O   Mosley Thomas H TH   Murabito Joanne M JM   Müller-Myhsok Bertram B   Nöthen Markus M MM   Nyholt Dale R DR   O'Donovan Michael C MC   Penninx Brenda W BW   Pergadia Michele L ML   Perlis Roy R   Potash James B JB   Preisig Martin M   Purcell Shaun M SM   Quiroz Jorge A JA   Räikkönen Katri K   Rice John P JP   Rietschel Marcella M   Rivera Margarita M   Schulze Thomas G TG   Shi Jianxin J   Shyn Stanley S   Sinnamon Grant C GC   Smit Johannes H JH   Smoller Jordan W JW   Snieder Harold H   Tanaka Toshiko T   Tansey Katherine E KE   Teumer Alexander A   Uher Rudolf R   Umbricht Daniel D   Van der Auwera Sandra S   Ware Erin B EB   Weir David R DR   Weissman Myrna M MM   Willemsen Gonneke G   Yang Jingyun J   Zhao Wei W   Tiemeier Henning H   Sullivan Patrick F PF  

Biological psychiatry 20161208 5

<h4>Background</h4>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.<h4>Methods</h4>We analyz  ...[more]

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