Background
Methods
Sample
Normal (n = 109) | Mean |
---|---|
Age (year) | 71.7 |
CSF Aβ1-42 levels (pg/ml) | 205.8 |
CSF P-tau181P levels (pg/ml) | 25.4 |
CSF T-tau levels (pg/ml) | 71.8 |
Last MMSE | 29 |
N
| |
Male | 59 |
Female | 50 |
MCI (n = 109)
|
Mean
|
Age (year) | 70 |
CSF Aβ1-42 levels (pg/ml) | 170.4 |
CSF P-tau181P levels (pg/ml) | 33.7 |
CSF T-tau level (pg/ml) | 99.5 |
Last MMSE | 26.5 |
N
| |
Male | 72 |
Female | 37 |
AD (n = 172)
|
Mean
|
Age (year) | 71 |
CSF Aβ1-42 levels (pg/ml) | 144.7 |
CSF P-tau181P levels (pg/ml) | 40.3 |
CSF T-tau levels (pg/ml) | 115.3 |
Last MMSE | 21.1 |
N
| |
Male | 105 |
Female | 67 |
APOEgenotype data (after removing outliers: n = 390) | |||||||
---|---|---|---|---|---|---|---|
APOEgenotype | ε2/ε2 | ε2/ε3 | ε2/ε4 | ε3/ε3 | ε3/4 | ε4/ε4 | |
Normal (n = 109) |
n
| 0 | 18 | 2 | 66 | 21 | 2 |
MCI (n = 109) |
n
| 0 | 10 | 2 | 47 | 40 | 10 |
AD (n = 172) |
n
| 0 | 1 | 3 | 54 | 81 | 33 |
APOE
allele
|
ε2
|
ε3
|
ε4
| ||||
Normal (n = 109) |
n
| 20 | 105 | 25 | |||
MCI (n = 109) |
n
| 12 | 97 | 52 | |||
AD (n = 172) |
n
| 4 | 136 | 117 | |||
APOE
genotype data before removing outliers: n = 410)
| |||||||
APOE
genotype
|
ε2/ε2
|
ε2/ε3
|
ε2/ε4
|
ε3/ε3
|
ε3/ε4
|
ε4/ε4
| |
Normal (n = 119) |
n
| 0 | 20 | 2 | 71 | 24 | 2 |
MCI (n = 115) |
n
| 0 | 10 | 2 | 52 | 41 | 10 |
AD (n = 176) |
n
| 0 | 2 | 3 | 54 | 83 | 34 |
APOE
allele
|
ε2
|
ε3
|
ε4
| ||||
Normal (n = 119) |
n
| 22 | 115 | 28 | |||
MCI (n = 115) |
n
| 12 | 103 | 53 | |||
AD (n = 176) |
n
| 5 | 139 | 120 |
Genotyping and sample quality control
Effect of APOEε4 copy number on CSF biomarker levels
Association testing of SNPs and CSF analysis
Gene ontology and E-SNP analysis
Results and Discussion
Association of SNPs with CSF biomarkers
Linear regression result without using covariates | ||||||||
---|---|---|---|---|---|---|---|---|
Normal: Aβ1-42
| ||||||||
Chromosome | SNP | Position | A1 | TEST | BETA | STAT | P-value | Gene Symbol, Gene Name |
15 | rs2899472 | 49303347 | A | GENO_2DF | NA | 40.21 | 1.86E-09 | CYP19A1, cytochrome p450, family 19, subfamily a, polypeptide 1 |
15 | rs2899472 | 49303347 | A | DOMDEV | 0.1791 | 5.859 | 5.40E-08 | CYP19A1, cytochrome p450, family 19, subfamily a, polypeptide 1 |
1 | rs11206801 | 56623274 | A | GENO_2DF | NA | 33.14 | 6.37E-08 | |
1 | rs4431886 | 56624855 | C | GENO_2DF | NA | 33.14 | 6.37E-08 | |
15 | rs2899472 | 49303347 | A | ADD | -0.1407 | -5.699 | 1.11E-07 | CYP19A1, cytochrome p450, family 19, subfamily a, polypeptide 1 |
19 | rs2075650 | 50087459 | G | GENO_2DF | NA | 30.02 | 3.03E-07 | TOMM40, translocase of outer mitochondrial membrane 40 homolog (yeast) |
12 | rs10784496 | 64447238 | G | GENO_2DF | NA | 29.98 | 3.09E-07 | |
7 | rs12534221 | 130938530 | A | GENO_2DF | NA | 27.83 | 9.04E-07 | |
6 | rs1727638 | 72196293 | A | GENO_2DF | NA | 27.69 | 9.71E-07 | |
Normal: T-tau
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
12 | rs1997111 | 117872301 | T | GENO_2DF | NA | 36.66 | 1.10E-08 | |
12 | rs11069178 | 117852210 | C | GENO_2DF | NA | 31.23 | 1.65E-07 | |
2 | rs17189298 | 119561787 | A | GENO_2DF | NA | 29.51 | 3.90E-07 | |
8 | rs2935776 | 109699079 | C | GENO_2DF | NA | 28.81 | 5.53E-07 | |
8 | rs2928826 | 109683270 | T | GENO_2DF | NA | 28.73 | 5.77E-07 | |
2 | rs895401 | 119584178 | G | GENO_2DF | NA | 27.86 | 8.90E-07 | |
2 | rs893769 | 119556554 | C | ADD | -0.1024 | -5.237 | 8.92E-07 | |
Normal: P-tau
181p
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
18 | rs1943816 | 69209602 | C | GENO_2DF | NA | 32.09 | 1.08E-07 | |
2 | rs2074955 | 158686040 | C | GENO_2DF | NA | 32.06 | 1.09E-07 | UPP2, uridine phosphorylase 2 |
MCI: T-tau
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
22 | rs5998432 | 31075916 | T | GENO_2DF | NA | 27.91 | 8.696E-07 | |
MCI: P-tau
181p
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
2 | rs7558386 | 227270383 | G | GENO_2DF | NA | 32.09 | 1.08E-07 | |
2 | rs7558386 | 227270383 | G | DOMDEV | 0.242 | 5.343 | 5.27E-07 | |
3 | rs7631605 | 37209593 | T | GENO_2DF | NA | 27.71 | 9.60E-07 | |
AD: Aβ
1-42
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
21 | rs239713 | 27618347 | T | GENO_2DF | NA | 29.03 | 4.96E-07 | |
AD: T-tau
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
20 | rs4925189 | 59380439 | G | DOMDEV | 0.1969 | 5.178 | 6.35E-07 | CDH4, cadherin 4, type 1, R-cadherin (retinal) |
AD: P-tau
181p
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
4 | rs12643654 | 96378840 | G | GENO_2DF | NA | 29.04 | 4.95E-07 | UNC5C, unc-5 homolog C (C. elegans) |
Linear regression result using APOE genotype and age as covariates
| ||||||||
Normal: Aβ
1-42
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
15 | rs2899472 | 49303347 | A | GENO_2DF | NA | 53.98 | 1.90E-12 | CYP19A1, cytochrome p450, family 19, subfamily a, polypeptide 1 |
15 | rs2899472 | 49303347 | A | ADD | -0.1393 | -6.925 | 3.85E- 0 | CYP19A1, cytochrome p450, family 19, subfamily a, polypeptide 1 |
15 | rs2899472 | 49303347 | A | DOMDEV | 0.1614 | 6.425 | 4.15E-09 | CYP19A1, cytochrome p450, family 19, subfamily a, polypeptide 1 |
21 | rs1022442 | 21277717 | A | GENO_2DF | NA | 30.21 | 2.75E-07 | NCAM2, neural cell adhesion molecule 2 |
10 | rs2493624 | 19102262 | G | GENO_2DF | NA | 28.61 | 6.14E-07 | |
10 | rs11015839 | 19042893 | A | GENO_2DF | NA | 28.51 | 6.45E-07 | ARL5B, adp-ribosylation factor-like 5b |
10 | rs11015860 | 19045045 | G | GENO_2DF | NA | 28.51 | 6.45E-07 | |
1 | rs10911736 | 183689227 | A | GENO_2DF | NA | 28.16 | 7.69E-07 | |
10 | rs11015839 | 19042893 | A | ADD | -0.1151 | -5.257 | 7.87E-07 | |
10 | rs11015860 | 19045045 | G | ADD | -0.1151 | -5.257 | 7.87E-07 | |
10 | rs11015939 | 19057948 | A | ADD | -0.1243 | -5.219 | 9.25E-07 | |
10 | rs2495832 | 19114467 | G | ADD | -0.1243 | -5.219 | 9.25E-07 | |
6 | rs12203791 | 67778209 | T | GENO_2DF | NA | 27.68 | 9.76E-07 | |
10 | rs10763625 | 19074957 | T | ADD | -0.124 | -5.206 | 9.78E-07 | |
Normal: T-tau
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
12 | rs1997111 | 117872301 | T | GENO_2DF | NA | 30.74 | 2.11E-07 | |
2 | rs17189298 | 119561787 | A | GENO_2DF | NA | 27.92 | 8.66E-07 | |
18 | rs1021599 | 28469054 | T | GENO_2DF | NA | 27.88 | 8.81E-07 | |
Normal: P-tau
181p
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
18 | rs1943816 | 69209602 | C | GENO_2DF | NA | 31.43 | 1.50E-07 | |
2 | rs2074955 | 158686040 | C | GENO_2DF | NA | 30.78 | 2.07E-07 | UPP2, uridine phosphorylase 2 |
MCI: Aβ
1-42
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
10 | rs2986971 | 30136634 | G | GENO_2DF | NA | 31.88 | 1.20E-07 | |
10 | rs2986971 | 30136634 | G | ADD | 0.08328 | 5.228 | 8.88E-07 | |
MCI: T-tau
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
4 | rs2768975 | 48724658 | G | GENO_2DF | NA | 30.89 | 1.96E-07 | FLJ21511, hypothetical protein flj21511 |
4 | rs6850199 | 48695607 | A | GENO_2DF | NA | 29.93 | 3.18E-07 | FLJ21511, hypothetical protein flj21511 |
18 | rs1445093 | 48024821 | C | GENO_2DF | NA | 28.14 | 7.75E-07 | |
MCI: P-tau
181p
| ||||||||
Chromosome
|
SNP
|
Position
|
A1
|
TEST
|
BETA
|
STAT
|
P-value
|
Gene Symbol, Gene Name
|
7 | rs121724 | 29207970 | G | GENO_2DF | NA | 31.49 | 1.45E-07 | CHN2, chimerin (chimaerin) 2 |
8 | rs7842088 | 17629409 | G | GENO_2DF | NA | 30.73 | 2.12E-07 | MTUS1, mitochondrial tumor suppressor 1 |