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

Song E. Kim; Han Na Kim; Yeo Jun Yun; Seong Gu Heo; Juhee Cho; Min Jung Kwon; Yoosoo Chang; Seungho Ryu; Hocheol Shin; Chol Shin; Nam H. Cho; Yeon Ah Sung; Hyung Lae Kim

doi:10.1038/jhg.2017.61

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

Song E. Kim, Han Na Kim, Yeo Jun Yun, Seong Gu Heo, Juhee Cho, Min Jung Kwon, Yoosoo Chang, Seungho Ryu, Hocheol Shin, Chol Shin, Nam H. Cho, Yeon Ah Sung, Hyung Lae Kim

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

14 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	903-909
Number of pages	7
Journal	Journal of Human Genetics
Volume	62
Issue number	10
DOIs	https://doi.org/10.1038/jhg.2017.61
Publication status	Published - 2017 Oct 1

ASJC Scopus subject areas

Genetics
Genetics(clinical)

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10.1038/jhg.2017.61

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Meta-analysis of genome-wide SNP- A nd pathway-based associations for facets of neuroticism. / Kim, Song E.; Kim, Han Na; Yun, Yeo Jun; Heo, Seong Gu; Cho, Juhee; Kwon, Min Jung; Chang, Yoosoo; Ryu, Seungho; Shin, Hocheol; Shin, Chol; Cho, Nam H.; Sung, Yeon Ah; Kim, Hyung Lae.

In: Journal of Human Genetics, Vol. 62, No. 10, 01.10.2017, p. 903-909.

Research output: Contribution to journal › Article › peer-review

@article{f2009ce1a79e44a1a27c28f5d6df4d5f,

title = "Meta-analysis of genome-wide SNP- A nd pathway-based associations for facets of neuroticism",

abstract = "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 {\^a} '9). Notable genes with suggestive associations (P<1.0 × 10 {\^a} '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.",

author = "Kim, {Song E.} and Kim, {Han Na} and Yun, {Yeo Jun} and Heo, {Seong Gu} and Juhee Cho and Kwon, {Min Jung} and Yoosoo Chang and Seungho Ryu and Hocheol Shin and Chol Shin and Cho, {Nam H.} and Sung, {Yeon Ah} and Kim, {Hyung Lae}",

note = "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). Publisher Copyright: {\textcopyright} 2017 The Japan Society of Human Genetics.",

year = "2017",

month = oct,

day = "1",

doi = "10.1038/jhg.2017.61",

language = "English",

volume = "62",

pages = "903--909",

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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). Publisher Copyright: © 2017 The Japan Society of Human Genetics.

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

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