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


  • 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=9.2610-9 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=2.3810-8). 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 (1.0910-12

published proceedings

  • JAMA Psychiatry

author list (cited authors)

  • Genetics of Personality Consortium, .., de Moor, M., van den Berg, S. M., Verweij, K., Krueger, R. F., Luciano, M., ... Boomsma, D. I.

complete list of authors

  • de Moor, Marleen HM||van den Berg, Stéphanie M||Verweij, Karin JH||Krueger, Robert F||Luciano, Michelle||Arias Vasquez, Alejandro||Matteson, Lindsay K||Derringer, Jaime||Esko, Tõnu||Amin, Najaf||Gordon, Scott D||Hansell, Narelle K||Hart, Amy B||Seppälä, Ilkka||Huffman, Jennifer E||Konte, Bettina||Lahti, Jari||Lee, Minyoung||Miller, Mike||Nutile, Teresa||Tanaka, Toshiko||Teumer, Alexander||Viktorin, Alexander||Wedenoja, Juho||Abecasis, Goncalo R||Adkins, Daniel E||Agrawal, Arpana||Allik, Jüri||Appel, Katja||Bigdeli, Timothy B||Busonero, Fabio||Campbell, Harry||Costa, Paul T||Davey Smith, George||Davies, Gail||de Wit, Harriet||Ding, Jun||Engelhardt, Barbara E||Eriksson, Johan G||Fedko, Iryna O||Ferrucci, Luigi||Franke, Barbara||Giegling, Ina||Grucza, Richard||Hartmann, Annette M||Heath, Andrew C||Heinonen, Kati||Henders, Anjali K||Homuth, Georg||Hottenga, Jouke-Jan||Iacono, William G||Janzing, Joost||Jokela, Markus||Karlsson, Robert||Kemp, John P||Kirkpatrick, Matthew G||Latvala, Antti||Lehtimäki, Terho||

publication date

  • January 1, 2015 11:11 AM