Journal
NATURE GENETICS
Volume 46, Issue 9, Pages 989-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3043
Keywords
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Categories
Funding
- MRC [MR/J004758/1, MC_PC_09003, G0701075, G0700943, G108/638, G0901254, MC_G0901330, G0802462, G1001253, MR/L016400/1, G1100479, G0802760, MC_G1000735] Funding Source: UKRI
- Alzheimers Research UK [ARUK-PhD2014-16] Funding Source: researchfish
- Medical Research Council [G0701075, G0901254, G0700943, MC_G1000735, MR/L016400/1, G0802760, MR/L501554/1, G0802462, G1001253, G1100479, G108/638, MR/J004758/1, MR/L010305/1, G1100643, MC_G0901330, MC_PC_09003] Funding Source: researchfish
- National Institute for Health Research [ACF-2012-17-017] Funding Source: researchfish
- Parkinson's UK [G-0909, J-0804, G-0907, F-1202] Funding Source: researchfish
- Intramural NIH HHS [Z01 AG000949-03, Z01 AG000932-01] Funding Source: Medline
- Medical Research Council [G0901254, G1100643, MC_PC_09003, MC_G0901330, G1100479, MR/J004758/1, MC_G1000735, MR/L016400/1, G108/638, G0700943, G0802462, G0701075, G0802760, G1001253, MR/L010305/1, MR/L501554/1] Funding Source: Medline
- NCATS NIH HHS [UL1TR000124, UL1 TR001108, UL1 TR000124] Funding Source: Medline
- NCI NIH HHS [R01CA141668] Funding Source: Medline
- NCRR NIH HHS [1KL2RR024154, 2UL1 RR024156] Funding Source: Medline
- NHGRI NIH HHS [R44 HG006981] Funding Source: Medline
- NHLBI NIH HHS [R01 HL120393] Funding Source: Medline
- NIA NIH HHS [AG16495, U24 AG056270, AG033193, U24 AG021886, R01 AG041797, AG031287, P30AG013846, AG025259, AG023629, P30AG024826, AG08122] Funding Source: Medline
- NIDDK NIH HHS [DK063491] Funding Source: Medline
- NINDS NIH HHS [P50 NS038377, R01 NS075321, NS17950, K02 NS073836, R01 NS088538, R01NS037167, P50NS071674, NS036630, R01 NS076843, P50 NS071674, NS060113, NS050487, U01 NS082151, 1K23NS070867, R01-NS-36960] Funding Source: Medline
- Parkinson's UK [G-0907, J-0804, F-1202, G-0909] Funding Source: Medline
- Wellcome Trust [083948/Z/07/Z, 085475, 090355, WT089698/Z/09/Z, 089698, 076113] Funding Source: Medline
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We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 x 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.
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