Large-scale replication and heterogeneity in Parkinson disease genetic loci
(2012) In Neurology 79(7). p.67-659- Abstract
OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.
METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.
RESULTS: In the overall... (More)
OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.
METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.
RESULTS: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.
CONCLUSION: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.
(Less)
- author
- author collaboration
- organization
- publishing date
- 2012-08-14
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aged, Alleles, Case-Control Studies, Female, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Parkinson Disease, Polymorphism, Single Nucleotide, Journal Article
- in
- Neurology
- volume
- 79
- issue
- 7
- pages
- 9 pages
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- pmid:22786590
- scopus:84865196862
- ISSN
- 1526-632X
- DOI
- 10.1212/WNL.0b013e318264e353
- language
- English
- LU publication?
- yes
- additional info
- Andreas Puschmann is part of Group Author
- id
- 29175224-3e2e-4dd3-a666-43c8f0174d63
- alternative location
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3414661/
- date added to LUP
- 2017-07-04 15:46:11
- date last changed
- 2024-09-16 04:34:00
@article{29175224-3e2e-4dd3-a666-43c8f0174d63, abstract = {{<p>OBJECTIVE: Eleven genetic loci have reached genome-wide significance in a recent meta-analysis of genome-wide association studies in Parkinson disease (PD) based on populations of Caucasian descent. The extent to which these genetic effects are consistent across different populations is unknown.</p><p>METHODS: Investigators from the Genetic Epidemiology of Parkinson's Disease Consortium were invited to participate in the study. A total of 11 SNPs were genotyped in 8,750 cases and 8,955 controls. Fixed as well as random effects models were used to provide the summary risk estimates for these variants. We evaluated between-study heterogeneity and heterogeneity between populations of different ancestry.</p><p>RESULTS: In the overall analysis, single nucleotide polymorphisms (SNPs) in 9 loci showed significant associations with protective per-allele odds ratios of 0.78-0.87 (LAMP3, BST1, and MAPT) and susceptibility per-allele odds ratios of 1.14-1.43 (STK39, GAK, SNCA, LRRK2, SYT11, and HIP1R). For 5 of the 9 replicated SNPs there was nominally significant between-site heterogeneity in the effect sizes (I(2) estimates ranged from 39% to 48%). Subgroup analysis by ethnicity showed significantly stronger effects for the BST1 (rs11724635) in Asian vs Caucasian populations and similar effects for SNCA, LRRK2, LAMP3, HIP1R, and STK39 in Asian and Caucasian populations, while MAPT rs2942168 and SYT11 rs34372695 were monomorphic in the Asian population, highlighting the role of population-specific heterogeneity in PD.</p><p>CONCLUSION: Our study allows insight to understand the distribution of newly identified genetic factors contributing to PD and shows that large-scale evaluation in diverse populations is important to understand the role of population-specific heterogeneity.</p>}}, author = {{Sharma, Manu and Ioannidis, John P A and Aasly, Jan O. and Annesi, Grazia and Brice, Alexis and Van Broeckhoven, Christine and Bertram, Lars and Bozi, Maria and Crosiers, David and Clarke, Carl E and Facheris, Maurizio and Farrer, Matthew and Garraux, Gaetan and Gispert, Suzana and Auburger, Georg and Vilariño-Güell, Carles and Hadjigeorgiou, Georgios M. and Hicks, Andrew A and Hattori, Nobutaka and Jeon, Beom S. and Lesage, Suzanne and Lill, Christina M. and Lin, Juei-Jueng and Lynch, Timothy and Lichtner, Peter and Lang, Anthony E and Mok, Vincent and Jasinska-Myga, Barbara and Mellick, George D. and Morrison, Karen E. and Opala, Grzegorz and Pramstaller, Peter P and Pichler, Irene and Park, Sung-Sup and Quattrone, Aldo and Rogaeva, Ekaterina and Ross, Owen A. and Stefanis, Leonidas and Stockton, Joanne D and Satake, Wataru and Silburn, Peter A. and Theuns, Jessie and Tan, Eng-King and Toda, Tatsushi and Tomiyama, Hiroyuki and Uitti, Ryan J. and Wirdefeldt, Karin and Wszolek, Zbigniew K and Xiromerisiou, Georgia and Puschmann, Andreas}}, issn = {{1526-632X}}, keywords = {{Aged; Alleles; Case-Control Studies; Female; Gene Frequency; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Genotype; Humans; Male; Middle Aged; Parkinson Disease; Polymorphism, Single Nucleotide; Journal Article}}, language = {{eng}}, month = {{08}}, number = {{7}}, pages = {{67--659}}, publisher = {{Lippincott Williams & Wilkins}}, series = {{Neurology}}, title = {{Large-scale replication and heterogeneity in Parkinson disease genetic loci}}, url = {{http://dx.doi.org/10.1212/WNL.0b013e318264e353}}, doi = {{10.1212/WNL.0b013e318264e353}}, volume = {{79}}, year = {{2012}}, }