Table 1 Discovery analysis: 115 SORL1 variants in 640 cases and 1268 controls

From: Characterization of pathogenic SORL1 genetic variants for association with Alzheimer’s disease: a clinical interpretation strategy

CADD score

N-variants in

burden test

Cases

With at least

one variant

Total 640

Controls

With at least one

variant

Total 1268

OR (95% CI)

P -value a (unadjusted)

A. Variant stratification according to sample MAF <0.01 and SIFT/Polyphen and CADD

 MAF <0.01

All variants

100

83

140

1.2 (0.9–1.6)

0.23

SIFT/Polyphen damaging

36

40

44

1.9 (1.2–2.9)

7.2 × 10−3

CADD 0–20

55

42

94

0.9 (0.6–1.3)

0.59

CADD 20–30

26

28

43

1.3 (0.78–2.1)

0.34

CADD >30

19

15

8

4.0 (1.7–9.0)

9.9 × 10−4

B. Variant stratification according to sample MAF and CADD

 MAF >0.01 (variants detected in >38 subjects in this sample)

0–20

13

640

1268

1.0 (1.0–1.1)

0.54

20–30

1

48

103

1.0 (0.7–1.3)

0.83

>30

1

17

44

0.8 (0.5–1.3)

0.29

 0.001<MAF <0.01 (variants detected in 3–38 subjects in this sample

0–20

7

27

47

1.2 (0.7–1.9)

0.54

20–30

3

18

24

1.5 (0.8–2.9)

0.21

>30

1

1

3

0.7 (0.1–5.5)

0.73

 0.0005<MAF <0.001 (variants detected in 2–3 subjects in this sample)

0–20

12

6

21

0.7 (0.3–1.4)

0.33

20–30

5

3

9

0.7 (0.2–2.4)

0.57

>30

2

1

3

0.7 (0.1–5.2)

0.70

 MAF <0.0005 (singletons in this sample)

0–20

36

9

26*

0.7 (0.4–1.4)

0.31

20–30

18

7

11

1.3 (0.5–3.3)

0.65

>30

16

14

2

11.3 (4.0–32.1)

4.9 × 10−6

>30 missense

11

9

2

8.7 (2.5–30.4)

7.2 × 10−4

>30 stop/frameshift

5

5

0

19.8 (3.1–126.8) b

1.7 × 10−3

C. Variant stratification of singleton variants according to protein domainc and CADD

 VPS10

0–20

5

1

4

0.6 (0.1–3.6)

0.54

20–30

6

6

0

19.3 (3.6–105.2) b

6.1 × 10−4

>30

4

3

1

6.6 (0.8–53.1)

7.6 × 10−2

 LDL A and B

0–20

10

3

7

0.9 (0.2–3.2)

0.81

20–30

4

0

4

0.22 (0.0–1.7) b

0.14

>30

8

7

1

10.8 (2.5–46.7)

1.5 × 10−3

 Fibronectin

0–20

3

0

3

0.2 (0.0–2.5) b

0.23

20–30

5

0

5

0.2 (0.0–1.4) b

0.11

>30

4

4

0

20.5 (2.6–164.5) b

4.5 × 10−3

  1. Variants were categorized according to the associated minor allele frequency in the sample and CADD score. For each category, multiple variants per individual were collapsed into one variant such that an odds ratio and an associated P-value could be calculated using the score-based SeqMeta burden test, while using gender as a covariate. LDL-Receptor, low-density lipoprotein receptor A and BOR; odds ratio; VPS10, Vacuolar Protein Sorting domain 10. No subject carried more than one singleton, with the exception of one control subject who carried two intronic singletons with CADD 0–20 (*).
  2. aAssociations that are significant after multiple testing correction are shown in bold (P<7.1 × 10−4).
  3. bResults for the odds ratios can be considered a one-step approximation to the maximum likelihood result, such that ORs of infinite have lower values when controls contribute no variants to the association.
Back to article page