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Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

ABSTRACT: IMPORTANCE:Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases). OBJECTIVES:To identify genetic variants associated with neuroticism by performing a meta-analysis of genome-wide association results based on 1000 Genomes imputation; to evaluate whether common genetic variants as assessed by single-nucleotide polymorphisms (SNPs) explain variation in neuroticism by estimating SNP-based heritability; and to examine whether SNPs that predict neuroticism also predict MDD. DESIGN, SETTING, AND PARTICIPANTS:Genome-wide association meta-analysis of 30 cohorts with genome-wide genotype, personality, and MDD data from the Genetics of Personality Consortium. The study included 63,661 participants from 29 discovery cohorts and 9786 participants from a replication cohort. Participants came from Europe, the United States, or Australia. Analyses were conducted between 2012 and 2014. MAIN OUTCOMES AND MEASURES:Neuroticism scores harmonized across all 29 discovery cohorts by item response theory analysis, and clinical MDD case-control status in 2 of the cohorts. RESULTS:A genome-wide significant SNP was found on 3p14 in MAGI1 (rs35855737; P?=?9.26?×?10-9 in the discovery meta-analysis). This association was not replicated (P?=?.32), but the SNP was still genome-wide significant in the meta-analysis of all 30 cohorts (P?=?2.38?×?10-8). Common genetic variants explain 15% of the variance in neuroticism. Polygenic scores based on the meta-analysis of neuroticism in 27 cohorts significantly predicted neuroticism (1.09?×?10-12?

SUBMITTER: Genetics of Personality Consortium 

PROVIDER: S-EPMC4667957 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Meta-analysis of Genome-wide Association Studies for Neuroticism, and the Polygenic Association With Major Depressive Disorder.

de Moor Marleen H M MH   van den Berg Stéphanie M SM   Verweij Karin J H KJ   Krueger Robert F RF   Luciano Michelle M   Arias Vasquez Alejandro A   Matteson Lindsay K LK   Derringer Jaime J   Esko Tõnu T   Amin Najaf N   Gordon Scott D SD   Hansell Narelle K NK   Hart Amy B AB   Seppälä Ilkka I   Huffman Jennifer E JE   Konte Bettina B   Lahti Jari J   Lee Minyoung M   Miller Mike M   Nutile Teresa T   Tanaka Toshiko T   Teumer Alexander A   Viktorin Alexander A   Wedenoja Juho J   Abecasis Goncalo R GR   Adkins Daniel E DE   Agrawal Arpana A   Allik Jüri J   Appel Katja K   Bigdeli Timothy B TB   Busonero Fabio F   Campbell Harry H   Costa Paul T PT   Davey Smith George G   Davies Gail G   de Wit Harriet H   Ding Jun J   Engelhardt Barbara E BE   Eriksson Johan G JG   Fedko Iryna O IO   Ferrucci Luigi L   Franke Barbara B   Giegling Ina I   Grucza Richard R   Hartmann Annette M AM   Heath Andrew C AC   Heinonen Kati K   Henders Anjali K AK   Homuth Georg G   Hottenga Jouke-Jan JJ   Iacono William G WG   Janzing Joost J   Jokela Markus M   Karlsson Robert R   Kemp John P JP   Kirkpatrick Matthew G MG   Latvala Antti A   Lehtimäki Terho T   Liewald David C DC   Madden Pamela A F PA   Magri Chiara C   Magnusson Patrik K E PK   Marten Jonathan J   Maschio Andrea A   Medland Sarah E SE   Mihailov Evelin E   Milaneschi Yuri Y   Montgomery Grant W GW   Nauck Matthias M   Ouwens Klaasjan G KG   Palotie Aarno A   Pettersson Erik E   Polasek Ozren O   Qian Yong Y   Pulkki-Råback Laura L   Raitakari Olli T OT   Realo Anu A   Rose Richard J RJ   Ruggiero Daniela D   Schmidt Carsten O CO   Slutske Wendy S WS   Sorice Rossella R   Starr John M JM   St Pourcain Beate B   Sutin Angelina R AR   Timpson Nicholas J NJ   Trochet Holly H   Vermeulen Sita S   Vuoksimaa Eero E   Widen Elisabeth E   Wouda Jasper J   Wright Margaret J MJ   Zgaga Lina L   Porteous David D   Minelli Alessandra A   Palmer Abraham A AA   Rujescu Dan D   Ciullo Marina M   Hayward Caroline C   Rudan Igor I   Metspalu Andres A   Kaprio Jaakko J   Deary Ian J IJ   Räikkönen Katri K   Wilson James F JF   Keltikangas-Järvinen Liisa L   Bierut Laura J LJ   Hettema John M JM   Grabe Hans J HJ   van Duijn Cornelia M CM   Evans David M DM   Schlessinger David D   Pedersen Nancy L NL   Terracciano Antonio A   McGue Matt M   Penninx Brenda W J H BW   Martin Nicholas G NG   Boomsma Dorret I DI  

JAMA psychiatry 20150701 7

<h4>Importance</h4>Neuroticism is a pervasive risk factor for psychiatric conditions. It genetically overlaps with major depressive disorder (MDD) and is therefore an important phenotype for psychiatric genetics. The Genetics of Personality Consortium has created a resource for genome-wide association analyses of personality traits in more than 63,000 participants (including MDD cases).<h4>Objectives</h4>To identify genetic variants associated with neuroticism by performing a meta-analysis of ge  ...[more]

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