Identification of novel risk loci, causal insights, and heritable risk for Parkinson’s disease: a meta-genome wide association study
Project Lead:
Analysis Methodology
“We performed the largest meta-GWAS of PD to date, involving the analysis of 7.8M SNPs in 37.7K cases, 18.6K UK Biobank proxy-cases (having a first degree relative with PD), and 1.4M controls. We carried out a meta-analysis of this GWAS data to nominate novel loci. We then evaluated heritable risk estimates and predictive models using this data. We also utilized large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type and biological pathway enrichments for the identified risk factors. Additionally we examined shared genetic risk between PD and other phenotypes of interest via genetic correlations followed by Mendelian randomization.”
Underlying Analyses
Analysis Type:
GWAS
Target Type:
Gene
Description:
Genome-wide association studies (GWASs) in Parkinson’s disease (PD) have increased the scope of biological knowledge about the disease over the past decade. We sought to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into disease etiology.
Tissue Type:
Unspecified
Source Data Type:
Genomics
Source Data Cohorts:
Web-Based Study of Parkinson's Disease (PDWBS) cohort described in Chang et al. 2017, System Genomics of Parkinson's Disease (SGPD), Baylor College of Medicine / University of Maryland, Finnish Parkinson’s, Harvard Biomarker Study (HBS), McGill Parkinson's, Oslo Parkinson's Disease Study, Parkinson's Disease Biomarkers Program (PDBP), Parkinson's Progression Markers Initiative (PPMI), Spanish Parkinson's (from IPDGC), Tubingen Parkinson's Disease cohort (CouragePD), Vance (dbGap phs000394), UK PDMED (CouragePD), UK BioBank (UKB), IPDGC (Nalls et al. 2014 discovery phase), NeuroX - dbGaP (phs000918.v1.p1)
Data Dictionary
| Field Name | Field Name Expanded | Short Description (optional) |
|---|---|---|
| SNP | Single Nucleotide Polymorphism ID | |
| CHR | Chromosome | |
| BP | Base Pair Position | |
| hgnc_symbol | HGNC symbol | |
| Effect allele | Effect allele | |
| Other allele | Other allele | |
| Effect allele frequency | Effect allele frequency | |
| OR | Odds Ratio | |
| Low 95% CI | Low 95% Confidence Interval | |
| High 95% CI | High 95% Confidence Interval | |
| Beta | Effect size | |
| SE | Standard error for beta | |
| P, fixed-effects | P-value from fixed-effects meta analysis | |
| P, COJO | p -value from conditional joint analysis approach | |
| P, conditional | P-value from standard conditional analysis in 23andMe | |
| P, random-effects | P-value from random-effects meta analysis | |
| I2, % | Index of heterogeneity | |
| gene_type | Gene type from GENCODE |
Nominated Targets
FCGR2A (gene)
ensembl_id: -
hgnc_symbol: FCGR2A
gene_type: protein-coding gene
SNP:
rs6658353
CHR:
1
BP:
161469054
Effect allele:
c
Other allele:
g
Effect allele frequency:
0.501
OR:
1.07
Low 95% CI:
1.05
High 95% CI:
1.09
Beta:
0.065
SE:
0.009
P fixed-effects:
6.1e-12
P COJO:
4690000000000
P conditional:
0.0000138
P random-effects:
0.0000371
I2 %:
40.2
gene_name:
FCGR2A
VAMP4 (gene)
ensembl_id: -
hgnc_symbol: VAMP4
gene_type: protein-coding gene
SNP:
rs11578699
CHR:
1
BP:
171719769
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.195
OR:
0.93
Low 95% CI:
0.91
High 95% CI:
0.95
Beta:
-0.07
SE:
0.012
P fixed-effects:
4.47e-9
P COJO:
4450000000
P conditional:
0.00263
P random-effects:
1.09e-7
I2 %:
5.1
gene_name:
VAMP4
KCNS3 (gene)
ensembl_id: -
hgnc_symbol: KCNS3
gene_type: protein-coding gene
SNP:
rs76116224
CHR:
2
BP:
18147848
Effect allele:
a
Other allele:
t
Effect allele frequency:
0.904
OR:
1.12
Low 95% CI:
1.08
High 95% CI:
1.16
Beta:
0.11
SE:
0.019
P fixed-effects:
1.27e-8
P COJO:
127000000
P conditional:
3.75e-7
P random-effects:
1.27e-8
I2 %:
0
gene_name:
KCNS3
KCNIP3 (gene)
ensembl_id: -
hgnc_symbol: KCNIP3
gene_type: protein-coding gene
SNP:
rs2042477
CHR:
2
BP:
96000943
Effect allele:
a
Other allele:
t
Effect allele frequency:
0.242
OR:
0.94
Low 95% CI:
0.92
High 95% CI:
0.96
Beta:
-0.066
SE:
0.012
P fixed-effects:
1.38e-8
P COJO:
148000000
P conditional:
0.0000349
P random-effects:
1.38e-8
I2 %:
0
gene_name:
KCNIP3
LINC00693 (transcript)
ensembl_id: -
hgnc_symbol: LINC00693
gene_type: non-coding RNA
SNP:
rs6808178
CHR:
3
BP:
28705690
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.379
OR:
1.07
Low 95% CI:
1.05
High 95% CI:
1.09
Beta:
0.066
SE:
0.01
P fixed-effects:
8.09e-12
P COJO:
7180000000000
P conditional:
0.0000884
P random-effects:
8.09e-12
I2 %:
0
gene_name:
LINC00693
KPNA1 (gene)
ensembl_id: -
hgnc_symbol: KPNA1
gene_type: protein-coding gene
SNP:
rs55961674
CHR:
3
BP:
122196892
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.172
OR:
1.09
Low 95% CI:
1.06
High 95% CI:
1.12
Beta:
0.086
SE:
0.013
P fixed-effects:
9.98e-12
P COJO:
8300000000000
P conditional:
0.0000028
P random-effects:
9.98e-12
I2 %:
0
gene_name:
KPNA1
MED12L (gene)
ensembl_id: -
hgnc_symbol: MED12L
gene_type: protein-coding gene
SNP:
rs11707416
CHR:
3
BP:
151108965
Effect allele:
a
Other allele:
t
Effect allele frequency:
0.367
OR:
0.94
Low 95% CI:
0.92
High 95% CI:
0.96
Beta:
-0.063
SE:
0.01
P fixed-effects:
1.13e-10
P COJO:
10200000000
P conditional:
0.000266
P random-effects:
1.77e-7
I2 %:
10.9
gene_name:
MED12L
SPTSSB (gene)
ensembl_id: -
hgnc_symbol: SPTSSB
gene_type: protein-coding gene
SNP:
rs1450522
CHR:
3
BP:
161077630
Effect allele:
a
Other allele:
g
Effect allele frequency:
0.674
OR:
0.94
Low 95% CI:
0.92
High 95% CI:
0.96
Beta:
-0.062
SE:
0.01
P fixed-effects:
5.01e-10
P COJO:
49000000000
P conditional:
0.000351
P random-effects:
0.0000227
I2 %:
24.6
gene_name:
SPTSSB
LCORL (gene)
ensembl_id: -
hgnc_symbol: LCORL
gene_type: protein-coding gene
SNP:
rs34025766
CHR:
4
BP:
17968811
Effect allele:
a
Other allele:
t
Effect allele frequency:
0.159
OR:
0.92
Low 95% CI:
0.9
High 95% CI:
0.94
Beta:
-0.084
SE:
0.013
P fixed-effects:
2.87e-10
P COJO:
28200000000
P conditional:
0.00000743
P random-effects:
2.87e-10
I2 %:
0
gene_name:
LCORL
CLCN3 (gene)
ensembl_id: -
hgnc_symbol: CLCN3
gene_type: protein-coding gene
SNP:
rs62333164
CHR:
4
BP:
170583157
Effect allele:
a
Other allele:
g
Effect allele frequency:
0.326
OR:
0.94
Low 95% CI:
0.92
High 95% CI:
0.96
Beta:
-0.064
SE:
0.01
P fixed-effects:
2e-10
P COJO:
17700000000
P conditional:
0.000051
P random-effects:
0.0000217
I2 %:
21.3
gene_name:
CLCN3
PAM (gene)
ensembl_id: -
hgnc_symbol: PAM
gene_type: protein-coding gene
SNP:
rs26431
CHR:
5
BP:
102365794
Effect allele:
c
Other allele:
g
Effect allele frequency:
0.703
OR:
1.06
Low 95% CI:
1.04
High 95% CI:
1.09
Beta:
0.062
SE:
0.01
P fixed-effects:
1.57e-9
P COJO:
1650000000
P conditional:
0.006
P random-effects:
2.36e-7
I2 %:
7.9
gene_name:
PAM
C5orf24 (gene)
ensembl_id: -
hgnc_symbol: C5orf24
gene_type: protein-coding gene
SNP:
rs11950533
CHR:
5
BP:
134199105
Effect allele:
a
Other allele:
c
Effect allele frequency:
0.102
OR:
0.91
Low 95% CI:
0.88
High 95% CI:
0.94
Beta:
-0.092
SE:
0.016
P fixed-effects:
7.16e-9
P COJO:
6730000000
P conditional:
0.000508
P random-effects:
2.68e-8
I2 %:
1.9
gene_name:
C5orf24
TRIM40 (gene)
ensembl_id: -
hgnc_symbol: TRIM40
gene_type: protein-coding gene
SNP:
rs9261484
CHR:
6
BP:
30108683
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.245
OR:
0.94
Low 95% CI:
0.92
High 95% CI:
0.96
Beta:
-0.064
SE:
0.011
P fixed-effects:
1.62e-8
P COJO:
143000000
P conditional:
0.00000126
P random-effects:
1.62e-8
I2 %:
0
gene_name:
TRIM40
RIMS1 (gene)
ensembl_id: -
hgnc_symbol: RIMS1
gene_type: protein-coding gene
SNP:
rs12528068
CHR:
6
BP:
72487762
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.284
OR:
1.07
Low 95% CI:
1.05
High 95% CI:
1.09
Beta:
0.066
SE:
0.01
P fixed-effects:
1.63e-10
P COJO:
17900000000
P conditional:
0.0000098
P random-effects:
1.63e-10
I2 %:
0
gene_name:
RIMS1
FYN (gene)
ensembl_id: -
hgnc_symbol: FYN
gene_type: protein-coding gene
SNP:
rs997368
CHR:
6
BP:
112243291
Effect allele:
a
Other allele:
g
Effect allele frequency:
0.805
OR:
1.07
Low 95% CI:
1.05
High 95% CI:
1.1
Beta:
0.071
SE:
0.012
P fixed-effects:
1.84e-9
P COJO:
1970000000
P conditional:
0.0000261
P random-effects:
1.84e-9
I2 %:
0
gene_name:
FYN
RPS12 (gene)
ensembl_id: -
hgnc_symbol: RPS12
gene_type: protein-coding gene
SNP:
rs75859381
CHR:
6
BP:
133210361
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.967
OR:
0.8
Low 95% CI:
0.75
High 95% CI:
0.86
Beta:
-0.221
SE:
0.034
P fixed-effects:
1.04e-10
P COJO:
967000000000
P conditional:
0.00000109
P random-effects:
1.04e-10
I2 %:
0
gene_name:
RPS12
UBAP2 (gene)
ensembl_id: -
hgnc_symbol: UBAP2
gene_type: protein-coding gene
SNP:
rs6476434
CHR:
9
BP:
34046391
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.734
OR:
0.94
Low 95% CI:
0.92
High 95% CI:
0.96
Beta:
-0.062
SE:
0.011
P fixed-effects:
6.58e-9
P COJO:
6560000000
P conditional:
0.000274
P random-effects:
6.58e-9
I2 %:
0
gene_name:
UBAP2
GBF1 (gene)
ensembl_id: -
hgnc_symbol: GBF1
gene_type: protein-coding gene
SNP:
rs10748818
CHR:
10
BP:
104015279
Effect allele:
a
Other allele:
g
Effect allele frequency:
0.851
OR:
0.92
Low 95% CI:
0.9
High 95% CI:
0.95
Beta:
-0.079
SE:
0.013
P fixed-effects:
1.05e-9
P COJO:
1230000000
P conditional:
0.00000747
P random-effects:
1.05e-9
I2 %:
0
gene_name:
GBF1
RNF141 (gene)
ensembl_id: -
hgnc_symbol: RNF141
gene_type: protein-coding gene
SNP:
rs7938782
CHR:
11
BP:
10558777
Effect allele:
a
Other allele:
g
Effect allele frequency:
0.878
OR:
1.09
Low 95% CI:
1.06
High 95% CI:
1.12
Beta:
0.087
SE:
0.015
P fixed-effects:
2.12e-9
P COJO:
1970000000
P conditional:
2.17e-7
P random-effects:
2.12e-9
I2 %:
0
gene_name:
RNF141
SCAF11 (gene)
ensembl_id: -
hgnc_symbol: SCAF11
gene_type: protein-coding gene
SNP:
rs7134559
CHR:
12
BP:
46419086
Effect allele:
t
Other allele:
c
Effect allele frequency:
0.404
OR:
0.95
Low 95% CI:
0.93
High 95% CI:
0.97
Beta:
-0.054
SE:
0.01
P fixed-effects:
3.96e-8
P COJO:
380000000
P conditional:
0.0169
P random-effects:
0.0000184
I2 %:
25.2
gene_name:
SCAF11