Supplementary data to:
The Alzheimer disease BIN1 locus as a modifier of GBA-associated Parkinson disease
Table 1 with references
SNPs selected for analysis in mild and severe GBA mutation carriers
SNP
Annotated
gene
rs10949703 PTPRN2
rs7800486
CACNA2D1
rs13272940 MCPH1
rs11792219 GADD45G
rs6860670
SV2C
rs4263397
BST1
rs10898685 RAB38
rs13403026 BIN1
a
Full name
(MIM#)
Protein-tyrosine
phosphatase, receptortype, n, polypeptide 2
(601698)
Calcium channel, voltagedependent, alpha-2/delta
subunit 1
(114204)
Microcephalin 1
(607117)
Growth arrest- and DNA
damage-inducible gene
GADD45, gamma
(604949)
Synaptic vesicle
glycoprotein 2C
(610291)
Bone marrow stromal cell
antigen 1
(600387)
Ras-associated protein
rab38
(606281)
Bridging integrator 1
(601248)
References in supplementary data file
P value in
GWAS
(model)
6.4x10-7
(Dominant)
Additional reason
for selectiona
May be active during
early development of
human brain (1).
1.1x10-5
(Dominant)
Several roles in the
nervous system and
synapses (2).
1.8x10-5
(Dominant)
Importance in human
brain development (3).
2.3x10-5
(Dominant)
Importance in human
brain development (4).
2.9x10-5
(Additive)
Associated with PD
and smoking (5).
1.1x10-4
(Dominant)
Associated with PD
(6).
1.9x10-4
(Dominant)
Family member of
RAB7L1, a suspected
PD gene (7).
Strongly associated
with Alzheimer’s
disease (8).
2.9x10-3
(Dominant)
References
1.
Abu-Amero KK, Kondkar AA, Salih MA et al. Partial chromosome 7 duplication with a phenotype
mimicking the HOXA1 spectrum disorder. Ophthalmic Genet 2013: 34: 90-96.
2.
Bauer CS, Tran-Van-Minh A, Kadurin I et al. A new look at calcium channel alpha2delta subunits.
Curr Opin Neurobiol 2010: 20: 563-571.
3.
Venkatesh T, Suresh PS. Emerging roles of MCPH1: Expedition from primary microcephaly to
cancer. Eur J Cell Biol 2014.
4.
Sultan FA, Sweatt JD. The role of the Gadd45 family in the nervous system: a focus on
neurodevelopment, neuronal injury, and cognitive neuroepigenetics. Adv Exp Med Biol 2013: 793: 81-119.
5.
Hill-Burns EM, Singh N, Ganguly P et al. A genetic basis for the variable effect of smoking/nicotine
on Parkinson's disease. Pharmacogenomics J 2013: 13: 530-537.
6.
Satake W, Nakabayashi Y, Mizuta I et al. Genome-wide association study identifies common variants
at four loci as genetic risk factors for Parkinson's disease. Nat Genet 2009: 41: 1303-1307.
7.
Grill B, Bienvenut WV, Brown HM et al. C. elegans RPM-1 regulates axon termination and
synaptogenesis through the Rab GEF GLO-4 and the Rab GTPase GLO-1. Neuron 2007: 55: 587-601.
8.
Seshadri S, Fitzpatrick AL, Ikram MA et al. Genome-wide analysis of genetic loci associated with
Alzheimer disease. JAMA 2010: 303: 1832-1840.
Supplementary table 1 – Top 20 SNPs from GWAS data associated with age at onset among 79 mild GBA mutation
carriers, dominant and additive models.
dbSNP rs
Associated Gene
MAF
HWE P
AAO AA, yrs
AAO Aa, yrs
AAO aa, yrs
p valuea
0.22
0.43
0.39
0.21
0.29
0.31
0.26
0.39
0.39
0.41
0.27
0.30
0.37
0.13
0.19
1.00
0.48
0.50
1.00
0.44
0.57
0.48
0.48
0.10
0.40
0.42
0.24
1.00
55.67
58.13
59.30
51.50
50.86
65.78
49.50
63.71
63.71
62.12
56.43
56.20
51.88
60.00
50.17
53.97
53.90
52.38
54.25
63.55
53.85
62.82
62.82
63.58
52.32
53.81
55.64
49.33
63.32
66.58
66.11
63.11
64.05
53.64
63.79
52.45
52.45
52.48
63.50
64.38
65.59
61.77
6.44E-07
5.12E-06
6.08E-06
9.75E-06
1.08E-05
1.08E-05
1.14E-05
1.15E-05
1.15E-05
1.28E-05
1.4E-05
1.49E-05
1.83E-05
1.91E-05
Dominant model
rs10949703
rs17151725
rs6015310
rs12913847
rs1342836
rs7800486
rs489969
rs974801
rs2285720
rs773566
rs4644991
rs17094670
rs13272940
rs17149372
PTPRN2
MAGI2
STX16
KLF13
RYR2
CACNA2D1
RYR2
TET2
TET2
MAGI3
SOX11
HTR7
MCPH1
SNX2
rs3766875
rs17267523
rs11792219
rs1246940
rs4329917
rs3804133
RYR2
GPC6
GADD45G
RPP40
PLCG2
LRRC16A
0.28
0.18
0.27
0.40
0.47
0.13
1.00
1.00
1.00
0.64
0.37
1.00
52.50
61.00
65.67
49.73
62.00
46.00
54.25
50.92
64.00
56.78
61.77
50.63
64.05
62.45
54.19
65.89
50.30
61.80
2.01E-05
2.06E-05
2.3E-05
2.32E-05
2.46E-05
3.14E-05
0.39
0.40
0.49
0.49
0.49
0.26
0.16
0.29
0.46
0.37
0.11
0.20
0.31
0.49
0.13
0.22
0.22
0.44
0.48
0.09
0.69
0.46
0.43
0.43
0.31
0.44
0.99
0.87
0.61
0.20
0.92
0.98
0.46
0.73
0.70
0.57
0.57
0.11
0.44
0.35
48.62
49.73
51.95
51.95
51.95
49.50
38.50
50.86
52.11
51.88
30.00
43.00
65.78
51.17
46.00
71.67
71.67
64.68
66.85
57.75
56.78
58.39
58.39
58.54
53.85
52.81
54.25
57.76
55.64
51.13
53.88
63.55
59.07
50.63
63.90
63.90
61.31
58.00
48.87
64.77
65.89
66.41
66.41
65.83
63.79
61.93
64.05
65.79
65.59
61.22
62.31
53.64
65.55
61.80
55.02
55.02
52.25
53.43
61.27
2.14E-06
2.46E-06
5.9E-06
5.9E-06
1.21E-05
1.21E-05
1.44E-05
1.61E-05
2.41E-05
2.45E-05
2.48E-05
2.66E-05
2.94E-05
2.94E-05
3.38E-05
3.53E-05
3.53E-05
3.71E-05
4.07E-05
4.58E-05
Additive model
rs6561137
rs1246940
rs12154701
rs17167582
rs7787720
rs489969
rs17503497
rs1342836
rs7795991
rs13272940
rs7236632
rs4809647
rs7800486
rs6860670
rs3804133
rs4268948
rs10178322
rs10520501
rs1380202
rs1677891
ENOX1
RPP40
ETV1
ETV1
ETV1
RYR2
RPL5
RYR2
ETV1
MCPH1
RSL24D1
SULF2
CACNA2D1
SV2C
LRRC16A
SNAR-C1
SNAR-C1
MGC45800
BCL11B
NAV3
MAF, minor allele frequency; HWE, Hardy-Weinberg Equilibrium; AAO, age at onset; AA, homozygous for the major
allele; Aa, heterozygous for the minor allele; aa, homozygous for the minor allele.
a
Uncorrected p value