Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease

Joanna M Biernacka, Sun Ju Chung, Sebastian M. Armasu, Kari S. Anderson, Christina M. Lill, Lars Bertram, J. E. Ahlskog, Laura Brighina, Roberta Frigerio, Demetrius M. Maraganore

Research output: Contribution to journalArticle

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Abstract

Introduction Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach. Methods We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP-pesticide interaction effects, we also performed exploratory analyses of gene-pesticide interactions at the gene level. Results None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP-level tests; α = 2.1E-06 for gene-level tests). Top results in the SNP-level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene-level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene-pesticide interactions reached statistical support in this genome-wide screen. Conclusion Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.

Original languageEnglish (US)
Pages (from-to)25-30
Number of pages6
JournalParkinsonism and Related Disorders
Volume32
DOIs
StatePublished - Nov 1 2016

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Gene-Environment Interaction
Pesticides
Parkinson Disease
Genome
Genes
Single Nucleotide Polymorphism
Environmental Exposure

Keywords

  • Gene-environment interaction
  • Genome wide association study
  • Parkinson's disease
  • Pesticide exposure

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. / Biernacka, Joanna M; Chung, Sun Ju; Armasu, Sebastian M.; Anderson, Kari S.; Lill, Christina M.; Bertram, Lars; Ahlskog, J. E.; Brighina, Laura; Frigerio, Roberta; Maraganore, Demetrius M.

In: Parkinsonism and Related Disorders, Vol. 32, 01.11.2016, p. 25-30.

Research output: Contribution to journalArticle

Biernacka, JM, Chung, SJ, Armasu, SM, Anderson, KS, Lill, CM, Bertram, L, Ahlskog, JE, Brighina, L, Frigerio, R & Maraganore, DM 2016, 'Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease', Parkinsonism and Related Disorders, vol. 32, pp. 25-30. https://doi.org/10.1016/j.parkreldis.2016.08.002
Biernacka, Joanna M ; Chung, Sun Ju ; Armasu, Sebastian M. ; Anderson, Kari S. ; Lill, Christina M. ; Bertram, Lars ; Ahlskog, J. E. ; Brighina, Laura ; Frigerio, Roberta ; Maraganore, Demetrius M. / Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. In: Parkinsonism and Related Disorders. 2016 ; Vol. 32. pp. 25-30.
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abstract = "Introduction Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach. Methods We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP-pesticide interaction effects, we also performed exploratory analyses of gene-pesticide interactions at the gene level. Results None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP-level tests; α = 2.1E-06 for gene-level tests). Top results in the SNP-level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene-level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene-pesticide interactions reached statistical support in this genome-wide screen. Conclusion Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.",
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T1 - Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease

AU - Biernacka, Joanna M

AU - Chung, Sun Ju

AU - Armasu, Sebastian M.

AU - Anderson, Kari S.

AU - Lill, Christina M.

AU - Bertram, Lars

AU - Ahlskog, J. E.

AU - Brighina, Laura

AU - Frigerio, Roberta

AU - Maraganore, Demetrius M.

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Introduction Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach. Methods We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP-pesticide interaction effects, we also performed exploratory analyses of gene-pesticide interactions at the gene level. Results None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP-level tests; α = 2.1E-06 for gene-level tests). Top results in the SNP-level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene-level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene-pesticide interactions reached statistical support in this genome-wide screen. Conclusion Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.

AB - Introduction Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach. Methods We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP-pesticide interaction effects, we also performed exploratory analyses of gene-pesticide interactions at the gene level. Results None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP-level tests; α = 2.1E-06 for gene-level tests). Top results in the SNP-level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene-level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene-pesticide interactions reached statistical support in this genome-wide screen. Conclusion Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.

KW - Gene-environment interaction

KW - Genome wide association study

KW - Parkinson's disease

KW - Pesticide exposure

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