TMPRSS9 and GRIN2B are associated with neuroticism: a genome-wide association study in a European sample.

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.

• Authors: Nagesh Aragam, Ke-Sheng Wang, James L Anderson, Xuefeng Liu
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 50 Issue 2 Pg. 250-6 (Jun 2013) ISSN: 1559-1166 [Electronic] United States
• PMID: 23229837 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Twin Study)

Chemical References

• NR2B NMDA receptor
• Receptors, N-Methyl-D-Aspartate
• Serine Endopeptidases
• serine endopeptidase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antisocial Personality Disorder (genetics)
• Anxiety Disorders (genetics)
• Australia
• Female
• Genome, Human
• Genome-Wide Association Study
• Humans
• Male
• Middle Aged
• Netherlands
• Neuroticism
• Polymorphism, Single Nucleotide
• Quantitative Trait, Heritable
• Receptors, N-Methyl-D-Aspartate (genetics)
• Serine Endopeptidases (genetics)
• White People (genetics)