Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease

Todd L. Edwards; William K. Scott; Cherylyn Almonte; Amber Burt; Eric H. Powell; Gary W. Beecham; Liyong Wang; Stephan Züchner; Ioanna Konidari; Gaofeng Wang; Carlos Singer; Fatta Nahab; Burton Scott; Jeffrey M. Stajich; Margaret Pericak-Vance; Jonathan Haines; Jeffery M. Vance; Eden R. Martin

doi:10.1111/j.1469-1809.2009.00560.x

Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease

Todd L. Edwards, William K. Scott, Cherylyn Almonte, Amber Burt, Eric H. Powell, Gary W. Beecham, Liyong Wang, Stephan Züchner, Ioanna Konidari, Gaofeng Wang, Carlos Singer, Fatta Nahab, Burton Scott, Jeffrey M. Stajich, Margaret Pericak-Vance, Jonathan Haines, Jeffery M. Vance, Eden R. Martin

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

329 Scopus citations

Abstract

Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome-wide significant, associations. In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p-value = 6.7 × 10^-8; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17-1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p-value = 5.6 × 10^-8; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62-0.79] T vs. C allele, PAR% = 8%) were genomewide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD.

Original language	English (US)
Pages (from-to)	97-109
Number of pages	13
Journal	Annals of Human Genetics
Volume	74
Issue number	2
DOIs	https://doi.org/10.1111/j.1469-1809.2009.00560.x
State	Published - Mar 2010

Keywords

Alpha-Synuclein
Association study
Microtubule associated protein tau
Parkinson disease

ASJC Scopus subject areas

Genetics(clinical)
Genetics

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Edwards, T. L., Scott, W. K., Almonte, C., Burt, A., Powell, E. H., Beecham, G. W., Wang, L., Züchner, S., Konidari, I., Wang, G., Singer, C., Nahab, F., Scott, B., Stajich, J. M., Pericak-Vance, M., Haines, J., Vance, J. M., & Martin, E. R. (2010). Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease. Annals of Human Genetics, 74(2), 97-109. https://doi.org/10.1111/j.1469-1809.2009.00560.x

Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease. / Edwards, Todd L.; Scott, William K.; Almonte, Cherylyn; Burt, Amber; Powell, Eric H.; Beecham, Gary W.; Wang, Liyong ; Züchner, Stephan; Konidari, Ioanna; Wang, Gaofeng ; Singer, Carlos; Nahab, Fatta; Scott, Burton; Stajich, Jeffrey M.; Pericak-Vance, Margaret; Haines, Jonathan; Vance, Jeffery M.; Martin, Eden R.

In: Annals of Human Genetics, Vol. 74, No. 2, 03.2010, p. 97-109.

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

Edwards, TL, Scott, WK, Almonte, C, Burt, A, Powell, EH, Beecham, GW , Wang, L , Züchner, S, Konidari, I, Wang, G , Singer, C, Nahab, F, Scott, B, Stajich, JM, Pericak-Vance, M, Haines, J, Vance, JM & Martin, ER 2010, 'Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease', Annals of Human Genetics, vol. 74, no. 2, pp. 97-109. https://doi.org/10.1111/j.1469-1809.2009.00560.x

Edwards, Todd L. ; Scott, William K. ; Almonte, Cherylyn ; Burt, Amber ; Powell, Eric H. ; Beecham, Gary W. ; Wang, Liyong ; Züchner, Stephan ; Konidari, Ioanna ; Wang, Gaofeng ; Singer, Carlos ; Nahab, Fatta ; Scott, Burton ; Stajich, Jeffrey M. ; Pericak-Vance, Margaret ; Haines, Jonathan ; Vance, Jeffery M. ; Martin, Eden R. / Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease. In: Annals of Human Genetics. 2010 ; Vol. 74, No. 2. pp. 97-109.

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abstract = "Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome-wide significant, associations. In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p-value = 6.7 × 10-8; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17-1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p-value = 5.6 × 10-8; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62-0.79] T vs. C allele, PAR% = 8%) were genomewide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD.",

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AU - Burt, Amber

AU - Powell, Eric H.

AU - Beecham, Gary W.

AU - Wang, Liyong

AU - Züchner, Stephan

AU - Konidari, Ioanna

AU - Wang, Gaofeng

AU - Singer, Carlos

AU - Nahab, Fatta

AU - Scott, Burton

AU - Stajich, Jeffrey M.

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AB - Parkinson disease (PD) is a chronic neurodegenerative disorder with a cumulative prevalence of greater than one per thousand. To date three independent genome-wide association studies (GWAS) have investigated the genetic susceptibility to PD. These studies implicated several genes as PD risk loci with strong, but not genome-wide significant, associations. In this study, we combined data from two previously published GWAS of Caucasian subjects with our GWAS of 604 cases and 619 controls for a joint analysis with a combined sample size of 1752 cases and 1745 controls. SNPs in SNCA (rs2736990, p-value = 6.7 × 10-8; genome-wide adjusted p = 0.0109, odds ratio (OR) = 1.29 [95% CI: 1.17-1.42] G vs. A allele, population attributable risk percent (PAR%) = 12%) and the MAPT region (rs11012, p-value = 5.6 × 10-8; genome-wide adjusted p = 0.0079, OR = 0.70 [95% CI: 0.62-0.79] T vs. C allele, PAR% = 8%) were genomewide significant. No other SNPs were genome-wide significant in this analysis. This study confirms that SNCA and the MAPT region are major genes whose common variants are influencing risk of PD.

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Genome-Wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for parkinson disease

Abstract

Keywords

ASJC Scopus subject areas

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