Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database

Christina M. Lill; Johannes T. Roehr; Matthew B. McQueen; Fotini K. Kavvoura; Sachin Bagade; Brit Maren M. Schjeide; Leif M. Schjeide; Esther Meissner; Ute Zauft; Nicole C. Allen; Tian Liu; Marcel Schilling; Kari J. Anderson; Gary Beecham; Daniela Berg; Joanna M. Biernacka; Alexis Brice; Anita L. DeStefano; Chuong B. Do; Nicholas Eriksson; Stewart A. Factor; Matthew J. Farrer; Tatiana Foroud; Thomas Gasser; Taye Hamza; John A. Hardy; Peter Heutink; Erin M. Hill-Burns; Christine Klein; Jeanne C. Latourelle; Demetrius M. Maraganore; Eden R. Martin; Maria Martinez; Richard H. Myers; Michael A. Nalls; Nathan Pankratz; Haydeh Payami; Wataru Satake; William K. Scott; Manu Sharma; Andrew B. Singleton; Kari Stefansson; Tatsushi Toda; Joyce Y. Tung; Jeffery Vance; Nick W. Wood; Cyrus P. Zabetian; Peter Young; Rudolph E. Tanzi; Muin J. Khoury; Frauke Zipp; Hans Lehrach; John P.A. Ioannidis; Lars Bertram

doi:10.1371/journal.pgen.1002548

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database

Christina M. Lill
, Johannes T. Roehr
, Matthew B. McQueen
, Fotini K. Kavvoura
, Sachin Bagade
, Brit Maren M. Schjeide
, Leif M. Schjeide
, Esther Meissner
, Ute Zauft
, Nicole C. Allen
, Tian Liu
, Marcel Schilling
, Kari J. Anderson
, Gary Beecham
, Daniela Berg
, Joanna M. Biernacka
, Alexis Brice
, Anita L. DeStefano
, Chuong B. Do
, Nicholas Eriksson

Stewart A. Factor, Matthew J. Farrer, Tatiana Foroud, Thomas Gasser, Taye Hamza, John A. Hardy, Peter Heutink, Erin M. Hill-Burns, Christine Klein, Jeanne C. Latourelle, Demetrius M. Maraganore, Eden R. Martin, Maria Martinez, Richard H. Myers, Michael A. Nalls, Nathan Pankratz, Haydeh Payami, Wataru Satake, William K. Scott, Manu Sharma, Andrew B. Singleton, Kari Stefansson, Tatsushi Toda, Joyce Y. Tung, Jeffery Vance, Nick W. Wood, Cyrus P. Zabetian, Peter Young, Rudolph E. Tanzi, Muin J. Khoury, Frauke Zipp, Hans Lehrach, John P.A. Ioannidis, Lars Bertram

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

472 Scopus citations

Abstract

More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of ~27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P>5×10^-8) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3×10^-8). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

Original language	English (US)
Article number	e1002548
Journal	PLoS genetics
Volume	8
Issue number	3
DOIs	https://doi.org/10.1371/journal.pgen.1002548
State	Published - Mar 2012

Bibliographical note

Funding Information:
CB Do, N Eriksson, and JY Tung are employed by 23andMe and own stock options in the company. MJ Farrer and Mayo Foundation received royalties from H.Lundbeck A/S and Isis Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a seminar at Genzyme. T Gasser has received consultancy fees from Cephalon and Merck-Serono, grants from Novartis, payments for lectures including service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono, UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has received consulting fees or honoraria from Eisai and his institute has received consulting fees or honoraria from Merck-Serono. DM Maraganore has received extramural research funding support from the National Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and Medtronic (observational studies of Parkinson's disease). DM Maraganore has also received intramural research funding support from the Mayo Clinic and from NorthShore University Health System. DM Maraganore filed a provisional patent for a method to predict Parkinson's disease. This provisional patent is unlicensed. He also filed a provisional patent for a method to treat neurodegenerative disorders. That provisional patent has been licensed to Alnylam Pharmaceuticals and DM Maraganore has received royalty payments in total of less than $20,000. K Stefansson has received grants from deCODE.

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Lill, C. M., Roehr, J. T., McQueen, M. B., Kavvoura, F. K., Bagade, S., Schjeide, B. M. M., Schjeide, L. M., Meissner, E., Zauft, U., Allen, N. C., Liu, T., Schilling, M., Anderson, K. J., Beecham, G., Berg, D., Biernacka, J. M., Brice, A., DeStefano, A. L., Do, C. B., ... Bertram, L. (2012). Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database. PLoS genetics, 8(3), Article e1002548. https://doi.org/10.1371/journal.pgen.1002548

Lill, CM, Roehr, JT, McQueen, MB, Kavvoura, FK, Bagade, S, Schjeide, BMM, Schjeide, LM, Meissner, E, Zauft, U, Allen, NC, Liu, T, Schilling, M, Anderson, KJ, Beecham, G, Berg, D, Biernacka, JM, Brice, A, DeStefano, AL, Do, CB, Eriksson, N, Factor, SA, Farrer, MJ, Foroud, T, Gasser, T, Hamza, T, Hardy, JA, Heutink, P, Hill-Burns, EM, Klein, C, Latourelle, JC, Maraganore, DM, Martin, ER, Martinez, M, Myers, RH, Nalls, MA, Pankratz, N, Payami, H, Satake, W, Scott, WK, Sharma, M, Singleton, AB, Stefansson, K, Toda, T, Tung, JY, Vance, J, Wood, NW, Zabetian, CP, Young, P, Tanzi, RE, Khoury, MJ, Zipp, F, Lehrach, H, Ioannidis, JPA & Bertram, L 2012, 'Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database', PLoS genetics, vol. 8, no. 3, e1002548. https://doi.org/10.1371/journal.pgen.1002548

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title = "Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database",

abstract = "More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of \textasciitilde{}27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P>5×10-8) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3×10-8). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.",

author = "Lill, \{Christina M.\} and Roehr, \{Johannes T.\} and McQueen, \{Matthew B.\} and Kavvoura, \{Fotini K.\} and Sachin Bagade and Schjeide, \{Brit Maren M.\} and Schjeide, \{Leif M.\} and Esther Meissner and Ute Zauft and Allen, \{Nicole C.\} and Tian Liu and Marcel Schilling and Anderson, \{Kari J.\} and Gary Beecham and Daniela Berg and Biernacka, \{Joanna M.\} and Alexis Brice and DeStefano, \{Anita L.\} and Do, \{Chuong B.\} and Nicholas Eriksson and Factor, \{Stewart A.\} and Farrer, \{Matthew J.\} and Tatiana Foroud and Thomas Gasser and Taye Hamza and Hardy, \{John A.\} and Peter Heutink and Hill-Burns, \{Erin M.\} and Christine Klein and Latourelle, \{Jeanne C.\} and Maraganore, \{Demetrius M.\} and Martin, \{Eden R.\} and Maria Martinez and Myers, \{Richard H.\} and Nalls, \{Michael A.\} and Nathan Pankratz and Haydeh Payami and Wataru Satake and Scott, \{William K.\} and Manu Sharma and Singleton, \{Andrew B.\} and Kari Stefansson and Tatsushi Toda and Tung, \{Joyce Y.\} and Jeffery Vance and Wood, \{Nick W.\} and Zabetian, \{Cyrus P.\} and Peter Young and Tanzi, \{Rudolph E.\} and Khoury, \{Muin J.\} and Frauke Zipp and Hans Lehrach and Ioannidis, \{John P.A.\} and Lars Bertram",

note = "Funding Information: CB Do, N Eriksson, and JY Tung are employed by 23andMe and own stock options in the company. MJ Farrer and Mayo Foundation received royalties from H.Lundbeck A/S and Isis Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a seminar at Genzyme. T Gasser has received consultancy fees from Cephalon and Merck-Serono, grants from Novartis, payments for lectures including service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono, UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has received consulting fees or honoraria from Eisai and his institute has received consulting fees or honoraria from Merck-Serono. DM Maraganore has received extramural research funding support from the National Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and Medtronic (observational studies of Parkinson's disease). DM Maraganore has also received intramural research funding support from the Mayo Clinic and from NorthShore University Health System. DM Maraganore filed a provisional patent for a method to predict Parkinson's disease. This provisional patent is unlicensed. He also filed a provisional patent for a method to treat neurodegenerative disorders. That provisional patent has been licensed to Alnylam Pharmaceuticals and DM Maraganore has received royalty payments in total of less than \$20,000. K Stefansson has received grants from deCODE. ",

year = "2012",

month = mar,

doi = "10.1371/journal.pgen.1002548",

language = "English (US)",

volume = "8",

journal = "PLoS genetics",

issn = "1553-7390",

publisher = "Public Library of Science",

number = "3",

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TY - JOUR

T1 - Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics

T2 - The PDgene database

AU - Lill, Christina M.

AU - Roehr, Johannes T.

AU - McQueen, Matthew B.

AU - Kavvoura, Fotini K.

AU - Bagade, Sachin

AU - Schjeide, Brit Maren M.

AU - Schjeide, Leif M.

AU - Meissner, Esther

AU - Zauft, Ute

AU - Allen, Nicole C.

AU - Liu, Tian

AU - Schilling, Marcel

AU - Anderson, Kari J.

AU - Beecham, Gary

AU - Berg, Daniela

AU - Biernacka, Joanna M.

AU - Brice, Alexis

AU - DeStefano, Anita L.

AU - Do, Chuong B.

AU - Eriksson, Nicholas

AU - Factor, Stewart A.

AU - Farrer, Matthew J.

AU - Foroud, Tatiana

AU - Gasser, Thomas

AU - Hamza, Taye

AU - Hardy, John A.

AU - Heutink, Peter

AU - Hill-Burns, Erin M.

AU - Klein, Christine

AU - Latourelle, Jeanne C.

AU - Maraganore, Demetrius M.

AU - Martin, Eden R.

AU - Martinez, Maria

AU - Myers, Richard H.

AU - Nalls, Michael A.

AU - Pankratz, Nathan

AU - Payami, Haydeh

AU - Satake, Wataru

AU - Scott, William K.

AU - Sharma, Manu

AU - Singleton, Andrew B.

AU - Stefansson, Kari

AU - Toda, Tatsushi

AU - Tung, Joyce Y.

AU - Vance, Jeffery

AU - Wood, Nick W.

AU - Zabetian, Cyrus P.

AU - Young, Peter

AU - Tanzi, Rudolph E.

AU - Khoury, Muin J.

AU - Zipp, Frauke

AU - Lehrach, Hans

AU - Ioannidis, John P.A.

AU - Bertram, Lars

N1 - Funding Information: CB Do, N Eriksson, and JY Tung are employed by 23andMe and own stock options in the company. MJ Farrer and Mayo Foundation received royalties from H.Lundbeck A/S and Isis Pharmaceuticals. In addition, MJ Farrer has received an honorarium for a seminar at Genzyme. T Gasser has received consultancy fees from Cephalon and Merck-Serono, grants from Novartis, payments for lectures including service on speakers' bureaus from Boehringer Ingelheim, Merck-Serono, UCB, and Valean, and holds patents NGFN2 and KASPP. JA Hardy has received consulting fees or honoraria from Eisai and his institute has received consulting fees or honoraria from Merck-Serono. DM Maraganore has received extramural research funding support from the National Institutes of Health (2R01 ES10751), the Michael J. Fox Foundation (Linked Efforts to Accelerate Parkinson Solutions Award, Edmond J. Safra Global Genetics Consortia Award), and from Alnylam Pharmaceuticals and Medtronic (observational studies of Parkinson's disease). DM Maraganore has also received intramural research funding support from the Mayo Clinic and from NorthShore University Health System. DM Maraganore filed a provisional patent for a method to predict Parkinson's disease. This provisional patent is unlicensed. He also filed a provisional patent for a method to treat neurodegenerative disorders. That provisional patent has been licensed to Alnylam Pharmaceuticals and DM Maraganore has received royalty payments in total of less than $20,000. K Stefansson has received grants from deCODE.

PY - 2012/3

Y1 - 2012/3

N2 - More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of ~27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P>5×10-8) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3×10-8). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

AB - More than 800 published genetic association studies have implicated dozens of potential risk loci in Parkinson's disease (PD). To facilitate the interpretation of these findings, we have created a dedicated online resource, PDGene, that comprehensively collects and meta-analyzes all published studies in the field. A systematic literature screen of ~27,000 articles yielded 828 eligible articles from which relevant data were extracted. In addition, individual-level data from three publicly available genome-wide association studies (GWAS) were obtained and subjected to genotype imputation and analysis. Overall, we performed meta-analyses on more than seven million polymorphisms originating either from GWAS datasets and/or from smaller scale PD association studies. Meta-analyses on 147 SNPs were supplemented by unpublished GWAS data from up to 16,452 PD cases and 48,810 controls. Eleven loci showed genome-wide significant (P>5×10-8) association with disease risk: BST1, CCDC62/HIP1R, DGKQ/GAK, GBA, LRRK2, MAPT, MCCC1/LAMP3, PARK16, SNCA, STK39, and SYT11/RAB25. In addition, we identified novel evidence for genome-wide significant association with a polymorphism in ITGA8 (rs7077361, OR 0.88, P = 1.3×10-8). All meta-analysis results are freely available on a dedicated online database (www.pdgene.org), which is cross-linked with a customized track on the UCSC Genome Browser. Our study provides an exhaustive and up-to-date summary of the status of PD genetics research that can be readily scaled to include the results of future large-scale genetics projects, including next-generation sequencing studies.

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JF - PLoS genetics

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ER -

Comprehensive research synopsis and systematic meta-analyses in Parkinson's disease genetics: The PDgene database

Abstract

Bibliographical note

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