Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

Int Parkinson Dis Genomics Consort, Wellcome Trust Case-Control Consor; Michael A. Nalls; Vincent Plagnol; Dena G. Hernandez; Manu Sharma; Una-Marie Sheerin; Mohamad Saad; Javier Simon-Sanchez; Claudia Schulte; Suzanne Lesage; Sigurlaug Sveinbjornsdottir; Sampath Arepalli; Roger Barker; Yoav Ben-Shlomo; Henk W. Berendse; Daniela Berg; Kailash Bhatia; Rob M. A. de Bie; Alessandro Biffi; Bas Bloem; Zoltan Bochdanovits; Michael Bonin; Jose M. Bras; Kathrin Brockmann; Janet Brooks; David J. Burn; Gavin Charlesworth; Honglei Chen; Patrick F. Chinnery; Sean Chong; Carl E. Clarke; Mark R. Cookson; J. Mark Cooper; Jean Christophe Corvol; Carl Counsell; Philippe Damier; Jean-Francois Dartigues; Panos Deloukas; Guenther Deuschl; David T. Dexter; Karin D. van Dijk; Allissa Dillman; Frank Durif; Alexandra Duerr; Sarah Edkins; Jonathan R. Evans; Thomas Foltynie; Jianjun Gao; Michelle Gardner; J. Raphael Gibbs; Colin Smith

doi:10.1016/S0140-6736(10)62345-8

Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

Int Parkinson Dis Genomics Consort, Wellcome Trust Case-Control Consor, Michael A. Nalls, Vincent Plagnol, Dena G. Hernandez, Manu Sharma, Una-Marie Sheerin, Mohamad Saad, Javier Simon-Sanchez, Claudia Schulte, Suzanne Lesage, Sigurlaug Sveinbjornsdottir, Sampath Arepalli, Roger Barker, Yoav Ben-Shlomo, Henk W. Berendse, Daniela Berg, Kailash Bhatia, Rob M. A. de Bie, Alessandro Biffi, Bas BloemZoltan Bochdanovits, Michael Bonin, Jose M. Bras, Kathrin Brockmann, Janet Brooks, David J. Burn, Gavin Charlesworth, Honglei Chen, Patrick F. Chinnery, Sean Chong, Carl E. Clarke, Mark R. Cookson, J. Mark Cooper, Jean Christophe Corvol, Carl Counsell, Philippe Damier, Jean-Francois Dartigues, Panos Deloukas, Guenther Deuschl, David T. Dexter, Karin D. van Dijk, Allissa Dillman, Frank Durif, Alexandra Duerr, Sarah Edkins, Jonathan R. Evans, Thomas Foltynie, Jianjun Gao, Michelle Gardner, J. Raphael Gibbs, Colin Smith

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

Abstract

Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease.

Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated.

Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk.

Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.

Original language	English
Pages (from-to)	641-649
Number of pages	9
Journal	The Lancet
Volume	377
Issue number	9766
DOIs	https://doi.org/10.1016/S0140-6736(10)62345-8
Publication status	Published - 19 Feb 2011

Access to Document

10.1016/S0140-6736(10)62345-8

Imputation of sequence variants for identification of genetic risks for Parkinson's disease a meta-analysis of genome-wide association studies
Published in final edited form as: Lancet. 2011 February 19; 377(9766): 641–649. doi:10.1016/S0140-6736(10)62345-8.
Accepted author manuscript, 742 KB

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2962345-8/fulltext

Cite this

Int Parkinson Dis Genomics Consort, Wellcome Trust Case-Control Consor, Nalls, M. A., Plagnol, V., Hernandez, D. G., Sharma, M., Sheerin, U.-M., Saad, M., Simon-Sanchez, J., Schulte, C., Lesage, S., Sveinbjornsdottir, S., Arepalli, S., Barker, R., Ben-Shlomo, Y., Berendse, H. W., Berg, D., Bhatia, K., de Bie, R. M. A., Biffi, A., ... Smith, C. (2011). Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. The Lancet, 377(9766), 641-649. https://doi.org/10.1016/S0140-6736(10)62345-8

@article{5d1e741c7a4c4789a7f1fdaaaaecb929,

title = "Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies",

abstract = "Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease.Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated.Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk.Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.",

author = "{Int Parkinson Dis Genomics Consort, Wellcome Trust Case-Control Consor} and Nalls, {Michael A.} and Vincent Plagnol and Hernandez, {Dena G.} and Manu Sharma and Una-Marie Sheerin and Mohamad Saad and Javier Simon-Sanchez and Claudia Schulte and Suzanne Lesage and Sigurlaug Sveinbjornsdottir and Sampath Arepalli and Roger Barker and Yoav Ben-Shlomo and Berendse, {Henk W.} and Daniela Berg and Kailash Bhatia and {de Bie}, {Rob M. A.} and Alessandro Biffi and Bas Bloem and Zoltan Bochdanovits and Michael Bonin and Bras, {Jose M.} and Kathrin Brockmann and Janet Brooks and Burn, {David J.} and Gavin Charlesworth and Honglei Chen and Chinnery, {Patrick F.} and Sean Chong and Clarke, {Carl E.} and Cookson, {Mark R.} and Cooper, {J. Mark} and Corvol, {Jean Christophe} and Carl Counsell and Philippe Damier and Jean-Francois Dartigues and Panos Deloukas and Guenther Deuschl and Dexter, {David T.} and {van Dijk}, {Karin D.} and Allissa Dillman and Frank Durif and Alexandra Duerr and Sarah Edkins and Evans, {Jonathan R.} and Thomas Foltynie and Jianjun Gao and Michelle Gardner and Gibbs, {J. Raphael} and Colin Smith",

year = "2011",

month = feb,

day = "19",

doi = "10.1016/S0140-6736(10)62345-8",

language = "English",

volume = "377",

pages = "641--649",

journal = "The Lancet",

issn = "0140-6736",

publisher = "Elsevier",

number = "9766",

}

Int Parkinson Dis Genomics Consort, Wellcome Trust Case-Control Consor, Nalls, MA, Plagnol, V, Hernandez, DG, Sharma, M, Sheerin, U-M, Saad, M, Simon-Sanchez, J, Schulte, C, Lesage, S, Sveinbjornsdottir, S, Arepalli, S, Barker, R, Ben-Shlomo, Y, Berendse, HW, Berg, D, Bhatia, K, de Bie, RMA, Biffi, A, Bloem, B, Bochdanovits, Z, Bonin, M, Bras, JM, Brockmann, K, Brooks, J, Burn, DJ, Charlesworth, G, Chen, H, Chinnery, PF, Chong, S, Clarke, CE, Cookson, MR, Cooper, JM, Corvol, JC, Counsell, C, Damier, P, Dartigues, J-F, Deloukas, P, Deuschl, G, Dexter, DT, van Dijk, KD, Dillman, A, Durif, F, Duerr, A, Edkins, S, Evans, JR, Foltynie, T, Gao, J, Gardner, M, Gibbs, JR & Smith, C 2011, 'Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies', The Lancet, vol. 377, no. 9766, pp. 641-649. https://doi.org/10.1016/S0140-6736(10)62345-8

Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies. / Int Parkinson Dis Genomics Consort, Wellcome Trust Case-Control Consor; Nalls, Michael A.; Plagnol, Vincent et al.
In: The Lancet, Vol. 377, No. 9766, 19.02.2011, p. 641-649.

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

TY - JOUR

T1 - Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

AU - Int Parkinson Dis Genomics Consort, Wellcome Trust Case-Control Consor

AU - Nalls, Michael A.

AU - Plagnol, Vincent

AU - Hernandez, Dena G.

AU - Sharma, Manu

AU - Sheerin, Una-Marie

AU - Saad, Mohamad

AU - Simon-Sanchez, Javier

AU - Schulte, Claudia

AU - Lesage, Suzanne

AU - Sveinbjornsdottir, Sigurlaug

AU - Arepalli, Sampath

AU - Barker, Roger

AU - Ben-Shlomo, Yoav

AU - Berendse, Henk W.

AU - Berg, Daniela

AU - Bhatia, Kailash

AU - de Bie, Rob M. A.

AU - Biffi, Alessandro

AU - Bloem, Bas

AU - Bochdanovits, Zoltan

AU - Bonin, Michael

AU - Bras, Jose M.

AU - Brockmann, Kathrin

AU - Brooks, Janet

AU - Burn, David J.

AU - Charlesworth, Gavin

AU - Chen, Honglei

AU - Chinnery, Patrick F.

AU - Chong, Sean

AU - Clarke, Carl E.

AU - Cookson, Mark R.

AU - Cooper, J. Mark

AU - Corvol, Jean Christophe

AU - Counsell, Carl

AU - Damier, Philippe

AU - Dartigues, Jean-Francois

AU - Deloukas, Panos

AU - Deuschl, Guenther

AU - Dexter, David T.

AU - van Dijk, Karin D.

AU - Dillman, Allissa

AU - Durif, Frank

AU - Duerr, Alexandra

AU - Edkins, Sarah

AU - Evans, Jonathan R.

AU - Foltynie, Thomas

AU - Gao, Jianjun

AU - Gardner, Michelle

AU - Gibbs, J. Raphael

AU - Smith, Colin

PY - 2011/2/19

Y1 - 2011/2/19

N2 - Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease.Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated.Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk.Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.

AB - Background Genome-wide association studies (GWAS) for Parkinson's disease have linked two loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel risk loci for Parkinson's disease.Methods We did a meta-analysis of datasets from five Parkinson's disease GWAS from the USA and Europe to identify loci associated with Parkinson's disease (discovery phase). We then did replication analyses of significantly associated loci in an independent sample series. Estimates of population-attributable risk were calculated from estimates from the discovery and replication phases combined, and risk-profile estimates for loci identified in the discovery phase were calculated.Findings The discovery phase consisted of 5333 case and 12 019 control samples, with genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of 7053 case and 9007 control samples. We identified 11 loci that surpassed the threshold for genome-wide significance (p<5x10(-8)). Six were previously identified loci (MAPT, SNCA, HLA-DRB5, BSTI, GAK and LRRK2) and five were newly identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The combined population-attributable risk was 60.3% (95% CI 43.7-69-3). In the risk-profile analysis, the odds ratio in the highest quintile of disease risk was 2.51 (95% CI 2.23-2.83) compared with 1.00 in the lowest quintile of disease risk.Interpretation These data provide an insight into the genetics of Parkinson's disease and the molecular cause of the disease and could provide future targets for therapies.

U2 - 10.1016/S0140-6736(10)62345-8

DO - 10.1016/S0140-6736(10)62345-8

M3 - Article

SN - 0140-6736

VL - 377

SP - 641

EP - 649

JO - The Lancet

JF - The Lancet

IS - 9766

ER -

Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies

Abstract

Access to Document

Fingerprint

Cite this