Journal of Molecular Neuroscience

, Volume 50, Issue 2, pp 250–256

TMPRSS9 and GRIN2B Are Associated with Neuroticism: a Genome-Wide Association Study in a European Sample

  • Nagesh Aragam
  • Ke-Sheng Wang
  • James L. Anderson
  • Xuefeng Liu
Article

DOI: 10.1007/s12031-012-9931-1

Cite this article as:
Aragam, N., Wang, KS., Anderson, J.L. et al. J Mol Neurosci (2013) 50: 250. doi:10.1007/s12031-012-9931-1

Abstract

Major depression disorder (MDD) is a complex and chronic disease that ranks fourth as cause of disability worldwide. About 14 million adults in the USA are believed to have MDD, and an estimated 75 % attempt suicide making MDD a major public health problem. Neuroticism has been recognized as an endophenotype of MDD; however, few genome-wide association (GWA) analyses of neuroticism as a quantitative trait have been reported to date. The aim of this study is to identify genome-wide genetic variants affecting neuroticism using a European sample. A linear regression model was used to analyze the association with neuroticism as a continuous trait in the Netherlands Study of Depression and Anxiety and Netherlands Twin Registry population-based sample of 2,748 individuals with Perlegen 600K single nucleotide polymorphisms (SNPs). In addition, the neuroticism-associated genes/loci of the top 20 SNPs (p < 10−4) were examined with anti-social personality disorder (ASPD) in an Australian twin family study. Through GWA analysis, 32 neuroticism-associated SNPs (p < 10−4) were identified. The most significant association was observed with SNP rs4806846 within the TMPRSS9 gene (p = 7.79 × 10−6) at 19p13.3. The next best signal was in GRIN2B gene (rs220549, p = 1.05 × 10−5) at 12p12. In addition, several SNPs within GRIN2B showed borderline associations with ASPD in the Australian sample. In conclusion, these results provide a possible genetic basis for the association with neuroticism. Our findings provide a basis for replication in other populations to elucidate the potential role of these genetic variants in neuroticism and MDD along with a possible relationship between ASPD and neuroticism.

Keywords

Neuroticism Major depressive disorder Anti-social personality disorder Genome-wide association TMPRSS9 GRIN2B 

Supplementary material

12031_2012_9931_MOESM1_ESM.doc (42 kb)
Table S1(DOC 42.5 kb)
12031_2012_9931_MOESM2_ESM.doc (38 kb)
Table S2(DOC 38 kb)

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Nagesh Aragam
    • 1
    • 2
  • Ke-Sheng Wang
    • 1
  • James L. Anderson
    • 1
  • Xuefeng Liu
    • 1
  1. 1.Department of Biostatistics and Epidemiology, College of Public HealthEast Tennessee State UniversityJohnson CityUSA
  2. 2.Department of Microbiology and Immunology, School of MedicineUniversity of North Carolina at Chapel HillChapel HillUSA