Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions

Najaf Amin, Jouke Jan Hottenga, Narelle K. Hansell, A. Cecile J.W. Janssens, Marleen H.M. De Moor, Pamela A.F. Madden, Irina V. Zorkoltseva, Brenda W. Penninx, Antonio Terracciano, Manuela Uda, Toshiko Tanaka, Tonu Esko, Anu Realo, Luigi Ferrucci, Michelle Luciano, Gail Davies, Andres Metspalu, Goncalo R. Abecasis, Ian J. Deary, Katri RaikkonenLaura J. Bierut, Paul T. Costa, Viatcheslav Saviouk, Gu Zhu, Anatoly V. Kirichenko, Aaron Isaacs, Yurii S. Aulchenko, Gonneke Willemsen, Andrew C. Heath, Michele L. Pergadia, Sarah E. Medland, Tatiana I. Axenovich, Eco De Geus, Grant W. Montgomery, Margaret J. Wright, Ben A. Oostra, Nicholas G. Martin, Dorret I. Boomsma, Cornelia M. Van Duijn

Research output: Contribution to journalArticle

Abstract

Personality traits are complex phenotypes related to psychosomatic health. Individually, various gene finding methods have not achieved much success in finding genetic variants associated with personality traits. We performed a meta-analysis of four genome-wide linkage scans (N=6149 subjects) of five basic personality traits assessed with the NEO Five-Factor Inventory. We compared the significant regions from the meta-analysis of linkage scans with the results of a meta-analysis of genome-wide association studies (GWAS) (N∼17 000). We found significant evidence of linkage of neuroticism to chromosome 3p14 (rs1490265, LOD=4.67) and to chromosome 19q13 (rs628604, LOD=3.55); of extraversion to 14q32 (ATGG002, LOD=3.3); and of agreeableness to 3p25 (rs709160, LOD=3.67) and to two adjacent regions on chromosome 15, including 15q13 (rs970408, LOD=4.07) and 15q14 (rs1055356, LOD=3.52) in the individual scans. In the meta-analysis, we found strong evidence of linkage of extraversion to 4q34, 9q34, 10q24 and 11q22, openness to 2p25, 3q26, 9p21, 11q24, 15q26 and 19q13 and agreeableness to 4q34 and 19p13. Significant evidence of association in the GWAS was detected between openness and rs677035 at 11q24 (P-value=2.6 × 10 -06, KCNJ1). The findings of our linkage meta-analysis and those of the GWAS suggest that 11q24 is a susceptible locus for openness, with KCNJ1 as the possible candidate gene.

Original languageEnglish (US)
Pages (from-to)876-882
Number of pages7
JournalEuropean Journal of Human Genetics
Volume21
Issue number8
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Keywords

  • GSMA
  • KCNJ1
  • Linkage
  • NEO
  • Personality

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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    Amin, N., Hottenga, J. J., Hansell, N. K., Janssens, A. C. J. W., De Moor, M. H. M., Madden, P. A. F., Zorkoltseva, I. V., Penninx, B. W., Terracciano, A., Uda, M., Tanaka, T., Esko, T., Realo, A., Ferrucci, L., Luciano, M., Davies, G., Metspalu, A., Abecasis, G. R., Deary, I. J., ... Van Duijn, C. M. (2013). Refining genome-wide linkage intervals using a meta-analysis of genome-wide association studies identifies loci influencing personality dimensions. European Journal of Human Genetics, 21(8), 876-882. https://doi.org/10.1038/ejhg.2012.263