TY - JOUR
T1 - Meta-analysis of genome-wide SNP- A nd pathway-based associations for facets of neuroticism
AU - Kim, Song E.
AU - Kim, Han Na
AU - Yun, Yeo Jun
AU - Heo, Seong Gu
AU - Cho, Juhee
AU - Kwon, Min Jung
AU - Chang, Yoosoo
AU - Ryu, Seungho
AU - Shin, Hocheol
AU - Shin, Chol
AU - Cho, Nam H.
AU - Sung, Yeon Ah
AU - Kim, Hyung Lae
N1 - Funding Information:
This research was supported by the National Research Foundation of Korea, funded by the Ministry of Education (NRF-2016R1A6A3A11932719) and Ministry of Science, ICT & Future Planning (NRF-2014R1A2A2A04006291) and a grant of Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C0072). The genotype data of Ansan Ansung cohort were gratefully made available by the Center for Genome Science, Korea National Institute of Health, Korea Centers for Disease Control and Prevention. It was also supported with the computing resources by Global Science experimental Data hub Center (GSDC) Project and Korea Research Environment Open NETwork (KREONET) in Korea Institute of Science and Technology Information (KISTI). SNP genotyping data is publicly available upon proper requesting process at the Clinical Omics Data Archive (CODA, http://coda.nih.go.kr).
PY - 2017/10/1
Y1 - 2017/10/1
N2 - Neuroticism is a heritable personality trait that is comprised of distinct sub-factors, or facets. Sub-factors of neuroticism are linked to different emotional states or psychiatric symptoms and studying the genetic variants associated with these facets may help reveal the biological mechanisms underlying psychiatric disorders. In the present study, a meta-analysis of genome-wide association studies for six facets of neuroticism was performed in 5584 participants from three cohorts. Additionally, a Gene Set Enrichment Analysis was conducted to find biological pathways associated with each facet. Six neuroticism facets (N1: Anxiety, N2: Angry hostility, N3: Depression, N4: Self-consciousness, N5: Impulsivity and N6: Vulnerability) were assessed using the Korean version of the Revised NEO Personality Inventory. In the single-nucleotide polymorphism-based analysis, results showed genome-wide significance for N2 within the MIR548H3 gene (rs1360001, P=4.14 × 10 â '9). Notable genes with suggestive associations (P<1.0 × 10 â '6) were ITPR1 for N1, WNT7A for N2, FGF10 and FHIT for N3, DDR1 for N4, VGLL4 for N5 and PTPRD for N6. In the pathway-based analysis, the axon guidance pathway was identified to be associated with multiple facets of neuroticism (N2, N4 and N6). The focal adhesion and extracellular matrix receptor interaction pathways were significantly associated with N2 and N3. Our findings revealed genetic influences and biological pathways that are associated with facets of neuroticism.
AB - Neuroticism is a heritable personality trait that is comprised of distinct sub-factors, or facets. Sub-factors of neuroticism are linked to different emotional states or psychiatric symptoms and studying the genetic variants associated with these facets may help reveal the biological mechanisms underlying psychiatric disorders. In the present study, a meta-analysis of genome-wide association studies for six facets of neuroticism was performed in 5584 participants from three cohorts. Additionally, a Gene Set Enrichment Analysis was conducted to find biological pathways associated with each facet. Six neuroticism facets (N1: Anxiety, N2: Angry hostility, N3: Depression, N4: Self-consciousness, N5: Impulsivity and N6: Vulnerability) were assessed using the Korean version of the Revised NEO Personality Inventory. In the single-nucleotide polymorphism-based analysis, results showed genome-wide significance for N2 within the MIR548H3 gene (rs1360001, P=4.14 × 10 â '9). Notable genes with suggestive associations (P<1.0 × 10 â '6) were ITPR1 for N1, WNT7A for N2, FGF10 and FHIT for N3, DDR1 for N4, VGLL4 for N5 and PTPRD for N6. In the pathway-based analysis, the axon guidance pathway was identified to be associated with multiple facets of neuroticism (N2, N4 and N6). The focal adhesion and extracellular matrix receptor interaction pathways were significantly associated with N2 and N3. Our findings revealed genetic influences and biological pathways that are associated with facets of neuroticism.
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U2 - 10.1038/jhg.2017.61
DO - 10.1038/jhg.2017.61
M3 - Article
C2 - 28615674
AN - SCOPUS:85029863891
VL - 62
SP - 903
EP - 909
JO - Journal of Human Genetics
JF - Journal of Human Genetics
SN - 1434-5161
IS - 10
ER -