Genome-wide association uncovers shared genetic effects among personality traits and mood states

Michelle Luciano, Jennifer E. Huffman, Alejandro Arias-Vásquez, Anna A.E. Vinkhuyzen, Christel M. Middeldorp, Ina Giegling, Antony Payton, Gail Davies, Lina Zgaga, Joost Janzing, Xiayi Ke, Tessel Galesloot, Annette M. Hartmann, William Ollier, Albert Tenesa, Caroline Hayward, Maaike Verhagen, Grant W. Montgomery, Jouke Jan Hottenga, Bettina KonteJohn M. Starr, Veronique Vitart, Pieter E. Vos, Pamela A.F. Madden, Gonneke Willemsen, Heike Konnerth, Michael A. Horan, David J. Porteous, Harry Campbell, Sita H. Vermeulen, Andrew C. Heath, Alan Wright, Ozren Polasek, Sanja B. Kovacevic, Nicholas D. Hastie, Barbara Franke, Dorret I. Boomsma, Nicholas G. Martin, Dan Rujescu, James F. Wilson, Jan Buitelaar, Neil Pendleton, Igor Rudan, Ian J. Deary

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Measures of personality and psychological distress are correlated and exhibit genetic covariance. We conducted univariate genome-wide SNP (∼2.5 million) and gene-based association analyses of these traits and examined the overlap in results across traits, including a prediction analysis of mood states using genetic polygenic scores for personality. Measures of neuroticism, extraversion, and symptoms of anxiety, depression, and general psychological distress were collected in eight European cohorts (n ranged 546-1,338; maximum total n=6,268) whose mean age ranged from 55 to 79 years. Meta-analysis of the cohort results was performed, with follow-up associations of the top SNPs and genes investigated in independent cohorts (n=527-6,032). Suggestive association (P=8×10-8) of rs1079196 in the FHIT gene was observed with symptoms of anxiety. Other notable associations (P<6.09×10-6) included SNPs in five genes for neuroticism (LCE3C, POLR3A, LMAN1L, ULK3, SCAMP2), KIAA0802 for extraversion, and NOS1 for general psychological distress. An association between symptoms of depression and rs7582472 (near to MGAT5 and NCKAP5) was replicated in two independent samples, but other replication findings were less consistent. Gene-based tests identified a significant locus on chromosome 15 (spanning five genes) associated with neuroticism which replicated (P<0.05) in an independent cohort. Support for common genetic effects among personality and mood (particularly neuroticism and depressive symptoms) was found in terms of SNP association overlap and polygenic score prediction. The variance explained by individual SNPs was very small (up to 1%) confirming that there are no moderate/large effects of common SNPs on personality and related traits. © 2012 Wiley Periodicals, Inc.

Original languageEnglish
Pages (from-to)684-695
Number of pages12
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume159 B
Issue number6
DOIs
StatePublished - Sep 2012
Externally publishedYes

Keywords

  • Anxiety
  • Depression
  • Extraversion
  • GWAS
  • Neuroticism

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