Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21

Chris C A Spencer; Vincent Plagnol; Amy Strange; Michelle Gardner; Coro Paisan-Ruiz; Gavin Band; Roger A Barker; Celine Bellenguez; Kailash Bhatia; Hannah Blackburn; Jennie M Blackwell; Elvira Bramon; Martin A Brown; Matthew A Brown; David Burn; Juan-Pablo Casas; Patrick F Chinnery; Carl E. Clarke; Aiden Corvin; Nicholas Craddock; Panos Deloukas; Sarah Edkins; Jonathan Evans; Colin Freeman; Emma Gray; John Hardy; Gavin Hudson; Sarah Hunt; Janusz Jankowski; Cordelia Langford; Andrew J Lees; Hugh S Markus; Mark I McCarthy; Christopher G Mathew; Karen E Morrison; Colin N A Palmer; Justin P Pearson; Leena Peltonen; Matti Pirinen; Robert Plomin; Simon Potter; Anna Rautanen; Stephen J Sawcer; Zhan Su; Richard C Trembath; Ananth C Viswanathan; Nigel W Williams; Huw R Morris; Peter Donnelly; Nicholas W Wood; UK Parkinson's Disease Consortium

doi:10.1093/hmg/ddq469

Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21

Chris C A Spencer, Vincent Plagnol, Amy Strange, Michelle Gardner, Coro Paisan-Ruiz, Gavin Band, Roger A Barker, Celine Bellenguez, Kailash Bhatia, Hannah Blackburn, Jennie M Blackwell, Elvira Bramon, Martin A Brown, Matthew A Brown, David Burn, Juan-Pablo Casas, Patrick F Chinnery, Carl E. Clarke, Aiden Corvin, Nicholas CraddockPanos Deloukas, Sarah Edkins, Jonathan Evans, Colin Freeman, Emma Gray, John Hardy, Gavin Hudson, Sarah Hunt, Janusz Jankowski, Cordelia Langford, Andrew J Lees, Hugh S Markus, Mark I McCarthy, Christopher G Mathew, Karen E Morrison, Colin N A Palmer, Justin P Pearson, Leena Peltonen, Matti Pirinen, Robert Plomin, Simon Potter, Anna Rautanen, Stephen J Sawcer, Zhan Su, Richard C Trembath, Ananth C Viswanathan, Nigel W Williams, Huw R Morris, Peter Donnelly, Nicholas W Wood, UK Parkinson's Disease Consortium

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Abstract

We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P<10(-4)). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P<10(-10)) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.

Original language	English
Pages (from-to)	345-53
Number of pages	9
Journal	Human Molecular Genetics
Volume	20
Issue number	2
DOIs	https://doi.org/10.1093/hmg/ddq469
Publication status	Published - 2011

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10.1093/hmg/ddq469Licence: CC BY-NC

Final Published VersionFinal published version, 208 KBLicence: CC BY-NC

A Systematic Investigation into the Pathogenesis and Course of Parkinson's Syndrome (Wellcome Trust and MRC Neurodegenerative Diseases Initiative) (Joint with University College London)
Alessi, D. (Investigator)
Medical Research Council
1/09/10 → 31/08/15
Project: Research

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Spencer, C. C. A., Plagnol, V., Strange, A., Gardner, M., Paisan-Ruiz, C., Band, G., Barker, R. A., Bellenguez, C., Bhatia, K., Blackburn, H., Blackwell, J. M., Bramon, E., Brown, M. A., Brown, M. A., Burn, D., Casas, J.-P., Chinnery, P. F., Clarke, C. E., Corvin, A., ... UK Parkinson's Disease Consortium (2011). Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21. Human Molecular Genetics, 20(2), 345-53. https://doi.org/10.1093/hmg/ddq469

@article{e0592a9db7d54c9a83c07a04c036dab8,

title = "Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21",

abstract = "We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P<10(-4)). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P<10(-10)) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.",

author = "Spencer, {Chris C A} and Vincent Plagnol and Amy Strange and Michelle Gardner and Coro Paisan-Ruiz and Gavin Band and Barker, {Roger A} and Celine Bellenguez and Kailash Bhatia and Hannah Blackburn and Blackwell, {Jennie M} and Elvira Bramon and Brown, {Martin A} and Brown, {Matthew A} and David Burn and Juan-Pablo Casas and Chinnery, {Patrick F} and Clarke, {Carl E.} and Aiden Corvin and Nicholas Craddock and Panos Deloukas and Sarah Edkins and Jonathan Evans and Colin Freeman and Emma Gray and John Hardy and Gavin Hudson and Sarah Hunt and Janusz Jankowski and Cordelia Langford and Lees, {Andrew J} and Markus, {Hugh S} and McCarthy, {Mark I} and Mathew, {Christopher G} and Morrison, {Karen E} and Palmer, {Colin N A} and Pearson, {Justin P} and Leena Peltonen and Matti Pirinen and Robert Plomin and Simon Potter and Anna Rautanen and Sawcer, {Stephen J} and Zhan Su and Trembath, {Richard C} and Viswanathan, {Ananth C} and Williams, {Nigel W} and Morris, {Huw R} and Peter Donnelly and Wood, {Nicholas W} and {UK Parkinson's Disease Consortium}",

year = "2011",

doi = "10.1093/hmg/ddq469",

language = "English",

volume = "20",

pages = "345--53",

journal = "Human Molecular Genetics",

issn = "1460-2083",

publisher = "Oxford University Press",

number = "2",

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Spencer, CCA, Plagnol, V, Strange, A, Gardner, M, Paisan-Ruiz, C, Band, G, Barker, RA, Bellenguez, C, Bhatia, K, Blackburn, H, Blackwell, JM, Bramon, E, Brown, MA, Brown, MA, Burn, D, Casas, J-P, Chinnery, PF, Clarke, CE, Corvin, A, Craddock, N, Deloukas, P, Edkins, S, Evans, J, Freeman, C, Gray, E, Hardy, J, Hudson, G, Hunt, S, Jankowski, J, Langford, C, Lees, AJ, Markus, HS, McCarthy, MI, Mathew, CG, Morrison, KE, Palmer, CNA, Pearson, JP, Peltonen, L, Pirinen, M, Plomin, R, Potter, S, Rautanen, A, Sawcer, SJ, Su, Z, Trembath, RC, Viswanathan, AC, Williams, NW, Morris, HR, Donnelly, P, Wood, NW & UK Parkinson's Disease Consortium 2011, 'Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21', Human Molecular Genetics, vol. 20, no. 2, pp. 345-53. https://doi.org/10.1093/hmg/ddq469

TY - JOUR

T1 - Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21

AU - Spencer, Chris C A

AU - Plagnol, Vincent

AU - Strange, Amy

AU - Gardner, Michelle

AU - Paisan-Ruiz, Coro

AU - Band, Gavin

AU - Barker, Roger A

AU - Bellenguez, Celine

AU - Bhatia, Kailash

AU - Blackburn, Hannah

AU - Blackwell, Jennie M

AU - Bramon, Elvira

AU - Brown, Martin A

AU - Brown, Matthew A

AU - Burn, David

AU - Casas, Juan-Pablo

AU - Chinnery, Patrick F

AU - Clarke, Carl E.

AU - Corvin, Aiden

AU - Craddock, Nicholas

AU - Deloukas, Panos

AU - Edkins, Sarah

AU - Evans, Jonathan

AU - Freeman, Colin

AU - Gray, Emma

AU - Hardy, John

AU - Hudson, Gavin

AU - Hunt, Sarah

AU - Jankowski, Janusz

AU - Langford, Cordelia

AU - Lees, Andrew J

AU - Markus, Hugh S

AU - McCarthy, Mark I

AU - Mathew, Christopher G

AU - Morrison, Karen E

AU - Palmer, Colin N A

AU - Pearson, Justin P

AU - Peltonen, Leena

AU - Pirinen, Matti

AU - Plomin, Robert

AU - Potter, Simon

AU - Rautanen, Anna

AU - Sawcer, Stephen J

AU - Su, Zhan

AU - Trembath, Richard C

AU - Viswanathan, Ananth C

AU - Williams, Nigel W

AU - Morris, Huw R

AU - Donnelly, Peter

AU - Wood, Nicholas W

AU - UK Parkinson's Disease Consortium

PY - 2011

Y1 - 2011

N2 - We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P<10(-4)). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P<10(-10)) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.

AB - We performed a genome-wide association study (GWAS) in 1705 Parkinson's disease (PD) UK patients and 5175 UK controls, the largest sample size so far for a PD GWAS. Replication was attempted in an additional cohort of 1039 French PD cases and 1984 controls for the 27 regions showing the strongest evidence of association (P<10(-4)). We replicated published associations in the 4q22/SNCA and 17q21/MAPT chromosome regions (P<10(-10)) and found evidence for an additional independent association in 4q22/SNCA. A detailed analysis of the haplotype structure at 17q21 showed that there are three separate risk groups within this region. We found weak but consistent evidence of association for common variants located in three previously published associated regions (4p15/BST1, 4p16/GAK and 1q32/PARK16). We found no support for the previously reported SNP association in 12q12/LRRK2. We also found an association of the two SNPs in 4q22/SNCA with the age of onset of the disease.

U2 - 10.1093/hmg/ddq469

DO - 10.1093/hmg/ddq469

M3 - Article

C2 - 21044948

SN - 1460-2083

VL - 20

SP - 345

EP - 353

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 2

ER -

Dissection of the genetics of Parkinson's disease identifies an additional association 5' of SNCA and multiple associated haplotypes at 17q21

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Projects

A Systematic Investigation into the Pathogenesis and Course of Parkinson's Syndrome (Wellcome Trust and MRC Neurodegenerative Diseases Initiative) (Joint with University College London)

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