Identification of Risk Loci for Parkinson Disease in Asians and Comparison of Risk Between Asians and Europeans: A Genome-Wide Association Study
Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian). To identify novel genome-wide significant loci for PD in Asian individua...
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| Vydané v: | JAMA neurology Ročník 77; číslo 6; s. 746 |
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| Hlavní autori: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
| Vydavateľské údaje: |
United States
01.06.2020
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| ISSN: | 2168-6157, 2168-6157 |
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| Abstract | Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian).
To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts.
Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria.
Genotypes of common variants, association with disease status, and polygenic risk scores.
Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12).
This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia. |
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| AbstractList | Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian).ImportanceLarge-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian).To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts.ObjectivesTo identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts.Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria.Design Setting, and ParticipantsGenome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria.Genotypes of common variants, association with disease status, and polygenic risk scores.Main Outcomes and MeasuresGenotypes of common variants, association with disease status, and polygenic risk scores.Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12).ResultsOf 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12).This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.Conclusions and RelevanceThis study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia. Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian). To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts. Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson's Disease Society Brain Bank Criteria. Genotypes of common variants, association with disease status, and polygenic risk scores. Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2C and WBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association for SV2C (rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21; P = 1.17 × 10-10 in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity at WBSCR17 (rs9638616; I2=67.1%; P = 3.40 × 10-3 for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%; P = 6.81 × 10-12). This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta-genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia. |
| Author | Mao, Chengjie Lim, Shen-Yang Chen, Yongping Liu, Jianjun Wu, Yih-Ru Koh, Woon-Puay Chao, Yinxia Tandiono, Moses Foo, Jia Nee Ng, Ebonne Y Jiang, Lulu Mok, Kin Y Peng, Rong Chung, Sun Ju Jeon, Beom S Mok, Vincent Xu, Yu-Ming Liu, Chunfeng Pei, Zhong Tan, Ai Huey Annuar, Azlina Ahmad Lin, Juei-Jueng Chew, Elaine Guo Yan Toda, Tatsushi Lim, Jia Lun Xu, Renshi Prakash, Kumar-M Khor, Chiea Chuen Nalls, Mike A Shang, Hui-Fang Mok, Shi Qi Tan, Eng-King Shi, Chang-He Satake, Wataru Tan, Louis C S Zhang, BaoRong Blauwendraat, Cornelis Lian, Michelle M Chan, Anne Y Y Meah, Wee-Yang Au, Wing-Lok Song, Kyuyoung Yan, Yaping Yang, Jing Chen, Ling |
| Author_xml | – sequence: 1 givenname: Jia Nee surname: Foo fullname: Foo, Jia Nee organization: Human Genetics, Genome Institute of Singapore, ASTAR, Singapore, Singapore – sequence: 2 givenname: Elaine Guo Yan surname: Chew fullname: Chew, Elaine Guo Yan organization: Human Genetics, Genome Institute of Singapore, ASTAR, Singapore, Singapore – sequence: 3 givenname: Sun Ju surname: Chung fullname: Chung, Sun Ju organization: Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea – sequence: 4 givenname: Rong surname: Peng fullname: Peng, Rong organization: Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China – sequence: 5 givenname: Cornelis surname: Blauwendraat fullname: Blauwendraat, Cornelis organization: Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland – sequence: 6 givenname: Mike A surname: Nalls fullname: Nalls, Mike A organization: Data Tecnica International LLC, Glen Echo, Maryland – sequence: 7 givenname: Kin Y surname: Mok fullname: Mok, Kin Y organization: Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, United Kingdom – sequence: 8 givenname: Wataru surname: Satake fullname: Satake, Wataru organization: Department of Neurology, The University of Tokyo Graduate School of Medicine, Bunkyo, Tokyo, Japan – sequence: 9 givenname: Tatsushi surname: Toda fullname: Toda, Tatsushi organization: Department of Neurology, The University of Tokyo Graduate School of Medicine, Bunkyo, Tokyo, Japan – sequence: 10 givenname: Yinxia surname: Chao fullname: Chao, Yinxia organization: Duke-National University of Singapore Medical School, Singapore, Singapore – sequence: 11 givenname: Louis C S surname: Tan fullname: Tan, Louis C S organization: Department of Neurology, National Neuroscience Institute, Singapore, Singapore – sequence: 12 givenname: Moses surname: Tandiono fullname: Tandiono, Moses organization: Human Genetics, Genome Institute of Singapore, ASTAR, Singapore, Singapore – sequence: 13 givenname: Michelle M surname: Lian fullname: Lian, Michelle M organization: Human Genetics, Genome Institute of Singapore, ASTAR, Singapore, Singapore – sequence: 14 givenname: Ebonne Y surname: Ng fullname: Ng, Ebonne Y organization: Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore – sequence: 15 givenname: Kumar-M surname: Prakash fullname: Prakash, Kumar-M organization: Department of Neurology, National Neuroscience Institute, Singapore General Hospital, Singapore, Singapore – sequence: 16 givenname: Wing-Lok surname: Au fullname: Au, Wing-Lok organization: Department of Neurology, National Neuroscience Institute, Singapore, Singapore – sequence: 17 givenname: Wee-Yang surname: Meah fullname: Meah, Wee-Yang organization: Human Genetics, Genome Institute of Singapore, ASTAR, Singapore, Singapore – sequence: 18 givenname: Shi Qi surname: Mok fullname: Mok, Shi Qi organization: Human Genetics, Genome Institute of Singapore, ASTAR, Singapore, Singapore – sequence: 19 givenname: Azlina Ahmad surname: Annuar fullname: Annuar, Azlina Ahmad organization: Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia – sequence: 20 givenname: Anne Y Y surname: Chan fullname: Chan, Anne Y Y organization: Margaret K. 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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32310270$$D View this record in MEDLINE/PubMed |
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| References | 32572178 - Nat Rev Neurol. 2020 Sep;16(9):461-462 32617903 - Intern Emerg Med. 2020 Aug;15(5):901-905 |
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| SubjectTerms | Aged Asian People - genetics Female Genetic Predisposition to Disease - genetics Genome-Wide Association Study Genotype Humans Male Membrane Glycoproteins - genetics Middle Aged N-Acetylgalactosaminyltransferases - genetics Nerve Tissue Proteins - genetics Parkinson Disease - genetics Polypeptide N-acetylgalactosaminyltransferase Risk Factors White People - genetics |
| Title | Identification of Risk Loci for Parkinson Disease in Asians and Comparison of Risk Between Asians and Europeans: A Genome-Wide Association Study |
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