Pathway analysis of genome‐wide association datasets of personality traits

Abstract

Although several genome-wide association (GWA) studies of human personality have been recently published, genetic variants that are highly associated with certain personality traits remain unknown, due to difficulty reproducing results. To further investigate these genetic variants, we assessed biological pathways using GWA datasets. Pathway analysis using GWA data was performed on 1089 Korean women whose personality traits were measured with the Revised NEO Personality Inventory for the 5-factor model of personality. A total of 1042 pathways containing 8297 genes were included in our study. Of these, 14 pathways were highly enriched with association signals that were validated in 1490 independent samples. These pathways include association of: Neuroticism with axon guidance [L1 cell adhesion molecule (L1CAM) interactions]; Extraversion with neuronal system and voltage-gated potassium channels; Agreeableness with L1CAM interaction, neurotransmitter receptor binding and downstream transmission in postsynaptic cells; and Conscientiousness with the interferon-gamma and platelet-derived growth factor receptor beta polypeptide pathways. Several genes that contribute to top-ranked pathways in this study were previously identified in GWA studies or by pathway analysis in schizophrenia or other neuropsychiatric disorders. Here we report the first pathway analysis of all five personality traits. Importantly, our analysis identified novel pathways that contribute to understanding the etiology of personality traits.

Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism

“…Axon guidance has also previously reported to be linked to a broad dimension of neuroticism. 16 Axon guidance is associated with neural developmental processes and hierarchically belongs to a developmental biology pathway in the REACTOME database. Our findings suggest that neural development processes pathway may be a shared genetic component of lower-level traits of neuroticism.…”

“… 8 Nevertheless, the facet-level pathway analysis herein replicated the neuroticism-associated pathways identified in our previous pathway-based association study on the NEO personality inventory. 16 These findings suggest that detection of the genetic influences of complex traits at the single SNP level is difficult and that the interactions and cooperative effects of the genes comprising biological pathways may play more important roles in complex traits, especially in behavioral phenotypes such as personality traits.…”

“… 15 Moreover, such pathway analysis investigates biological pathways that are functionally important for cellular and molecular processes and may provide information on the underlying biological mechanisms of complex traits. This method has the advantages of increased effect size and statistical power and can be used to identify the biological pathways associated with personality 16 and neuropsychiatric phenotypes including schizophrenia. 17 …”

A genome‐wide association study of coping behaviors suggests FBXO45 is associated with emotional expression

“…Therefore, associations between coping behaviors and genetic effects consisting of multiple weak associations may be missed by conventional GWAS analysis. To improve the chances of identifying such associations, a pathway analysis or gene‐based analysis may be useful . Such methods can also provide additional insights into the functional and biological mechanisms underlying coping behavior personalities.…”

“…To improve the chances of identifying such associations, a pathway analysis or gene-based analysis may be useful. 17,18 Such methods can also provide additional insights into the functional and biological mechanisms underlying coping behavior personalities.…”