Genome-wide pathway analysis of a genome-wide association study on Alzheimer’s disease

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

The aims of this study were to identify candidate single nucleotide polymorphisms (SNPs) and mechanisms of Alzheimer’s disease (AD) and to generate SNP to gene to pathway hypotheses. An AD genome-wide association study (GWAS) dataset that included 370,542 SNPs in 1,000 cases and 1,000 controls of European descent was used in this study. Identify Candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 3 candidate SNPs and 2 pathways, which provided 3 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was rs8076604 [non-synonymous coding (deleterious)] to MYO18A to negative regulation of programmed cell death [nominal P < 0.001, false discovery rate (FDR) <0.043]. The second was rs2811226 (regulatory region) to ANXA1 to negative regulation of programmed cell death (nominal P < 0.001, FDR 0.043). The third was rs3734166 (non-synonymous coding) to CDC25C to M phase of the mitotic cell cycle (nominal P < 0.001, FDR 0.049). By applying the ICSNPathway analysis to the AD GWAS meta-analysis data, three candidate SNPs, three genes (MYO18A, ANXA1, CDC25C), 2 pathways involving negative regulation of programmed cell death and 1 pathway involving the M phase of the mitotic cell cycle were identified, which may contribute to AD susceptibility.

Original languageEnglish
Pages (from-to)53-59
Number of pages7
JournalNeurological Sciences
Volume36
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

Genome-Wide Association Study
Single Nucleotide Polymorphism
Alzheimer Disease
Genome
Cell Death
Mitosis
Cell Cycle
Nucleic Acid Regulatory Sequences
Disease Susceptibility
Genes
Meta-Analysis

Keywords

  • Alzheimer’s disease
  • Genome-wide association study
  • Pathway-based analysis

ASJC Scopus subject areas

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Genome-wide pathway analysis of a genome-wide association study on Alzheimer’s disease. / Lee, Young Ho; Song, Gwan Gyu.

In: Neurological Sciences, Vol. 36, No. 1, 01.01.2014, p. 53-59.

Research output: Contribution to journalArticle

@article{e7a26c1daf0344098cdb2f38a1846214,
title = "Genome-wide pathway analysis of a genome-wide association study on Alzheimer’s disease",
abstract = "The aims of this study were to identify candidate single nucleotide polymorphisms (SNPs) and mechanisms of Alzheimer’s disease (AD) and to generate SNP to gene to pathway hypotheses. An AD genome-wide association study (GWAS) dataset that included 370,542 SNPs in 1,000 cases and 1,000 controls of European descent was used in this study. Identify Candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 3 candidate SNPs and 2 pathways, which provided 3 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was rs8076604 [non-synonymous coding (deleterious)] to MYO18A to negative regulation of programmed cell death [nominal P < 0.001, false discovery rate (FDR) <0.043]. The second was rs2811226 (regulatory region) to ANXA1 to negative regulation of programmed cell death (nominal P < 0.001, FDR 0.043). The third was rs3734166 (non-synonymous coding) to CDC25C to M phase of the mitotic cell cycle (nominal P < 0.001, FDR 0.049). By applying the ICSNPathway analysis to the AD GWAS meta-analysis data, three candidate SNPs, three genes (MYO18A, ANXA1, CDC25C), 2 pathways involving negative regulation of programmed cell death and 1 pathway involving the M phase of the mitotic cell cycle were identified, which may contribute to AD susceptibility.",
keywords = "Alzheimer’s disease, Genome-wide association study, Pathway-based analysis",
author = "Lee, {Young Ho} and Song, {Gwan Gyu}",
year = "2014",
month = "1",
day = "1",
doi = "10.1007/s10072-014-1885-3",
language = "English",
volume = "36",
pages = "53--59",
journal = "Neurological Sciences",
issn = "1590-1874",
publisher = "Springer-Verlag Italia",
number = "1",

}

TY - JOUR

T1 - Genome-wide pathway analysis of a genome-wide association study on Alzheimer’s disease

AU - Lee, Young Ho

AU - Song, Gwan Gyu

PY - 2014/1/1

Y1 - 2014/1/1

N2 - The aims of this study were to identify candidate single nucleotide polymorphisms (SNPs) and mechanisms of Alzheimer’s disease (AD) and to generate SNP to gene to pathway hypotheses. An AD genome-wide association study (GWAS) dataset that included 370,542 SNPs in 1,000 cases and 1,000 controls of European descent was used in this study. Identify Candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 3 candidate SNPs and 2 pathways, which provided 3 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was rs8076604 [non-synonymous coding (deleterious)] to MYO18A to negative regulation of programmed cell death [nominal P < 0.001, false discovery rate (FDR) <0.043]. The second was rs2811226 (regulatory region) to ANXA1 to negative regulation of programmed cell death (nominal P < 0.001, FDR 0.043). The third was rs3734166 (non-synonymous coding) to CDC25C to M phase of the mitotic cell cycle (nominal P < 0.001, FDR 0.049). By applying the ICSNPathway analysis to the AD GWAS meta-analysis data, three candidate SNPs, three genes (MYO18A, ANXA1, CDC25C), 2 pathways involving negative regulation of programmed cell death and 1 pathway involving the M phase of the mitotic cell cycle were identified, which may contribute to AD susceptibility.

AB - The aims of this study were to identify candidate single nucleotide polymorphisms (SNPs) and mechanisms of Alzheimer’s disease (AD) and to generate SNP to gene to pathway hypotheses. An AD genome-wide association study (GWAS) dataset that included 370,542 SNPs in 1,000 cases and 1,000 controls of European descent was used in this study. Identify Candidate Causal SNPs and Pathway (ICSNPathway) analysis was applied to the GWAS dataset. ICSNPathway analysis identified 3 candidate SNPs and 2 pathways, which provided 3 hypothetical biological mechanisms. The strongest hypothetical biological mechanism was rs8076604 [non-synonymous coding (deleterious)] to MYO18A to negative regulation of programmed cell death [nominal P < 0.001, false discovery rate (FDR) <0.043]. The second was rs2811226 (regulatory region) to ANXA1 to negative regulation of programmed cell death (nominal P < 0.001, FDR 0.043). The third was rs3734166 (non-synonymous coding) to CDC25C to M phase of the mitotic cell cycle (nominal P < 0.001, FDR 0.049). By applying the ICSNPathway analysis to the AD GWAS meta-analysis data, three candidate SNPs, three genes (MYO18A, ANXA1, CDC25C), 2 pathways involving negative regulation of programmed cell death and 1 pathway involving the M phase of the mitotic cell cycle were identified, which may contribute to AD susceptibility.

KW - Alzheimer’s disease

KW - Genome-wide association study

KW - Pathway-based analysis

UR - http://www.scopus.com/inward/record.url?scp=84936986213&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84936986213&partnerID=8YFLogxK

U2 - 10.1007/s10072-014-1885-3

DO - 10.1007/s10072-014-1885-3

M3 - Article

C2 - 25037741

AN - SCOPUS:84936986213

VL - 36

SP - 53

EP - 59

JO - Neurological Sciences

JF - Neurological Sciences

SN - 1590-1874

IS - 1

ER -