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Table 5 Hippocampal sclerosis (HS) odds ratios for risk variants with and without adjustment for LATE-NC status

From: Analysis of genes (TMEM106B, GRN, ABCC9, KCNMB2, and APOE) implicated in risk for LATE-NC and hippocampal sclerosis provides pathogenetic insights: a retrospective genetic association study

Gene

MOI

SNV

Effect Allele

LATE-NC Adjusted

NACC

ROSMAP

Meta-Analysis

OR

P-value

OR

P-value

OR

95% CI

P-value

TMEM106B

Additive

rs1990622

A

Yes

1.23

0.396

1.61

0.017

1.44

(1.07, 1.95)

0.017

No

1.43

0.044

1.55

0.019

1.49

(1.15, 1.91)

0.002

TMEM106B

Additive

rs7781670

C

Yes

1.20

0.456

1.53

0.029

1.39

(1.03, 1.88)

0.030

No

1.47

0.034

1.50

0.028

1.48

(1.15, 1.91)

0.002

GRN

Additive

rs5848

T

Yes

1.37

0.168

1.37

0.123

1.37

(1.02, 1.84)

0.039

No

1.67

0.004

1.43

0.057

1.56

(1.21, 2.00)

< 0.001

ABCC9

Additive

rs1914361

G

Yes

1.92

0.005

1.31

0.152

1.52

(1.14, 2.03)

0.004

No

1.64

0.004

1.35

0.092

1.49

(1.17, 1.90)

0.001

ABCC9

Recessive

rs1914361

G

Yes

3.87

< 0.001

1.58

0.124

2.23

(1.42, 3.51)

< 0.001

No

2.69

< 0.001

1.64

0.075

2.12

(1.45, 3.09)

< 0.001

ABCC9

Additive

rs704178

G

Yes

1.51

0.079

1.52

0.034

1.52

(1.13, 2.04)

0.006

No

1.09

0.618

1.42

0.059

1.23

(0.96, 1.57)

0.099

ABCC9

Recessive

rs704178

G

Yes

1.77

0.121

1.48

0.171

1.58

(1.02, 2.47)

0.042

No

1.33

0.292

1.43

0.180

1.38

(0.95, 2.01)

0.090

APOE

Additive

rs769449

A

Yes

1.15

0.589

1.54

0.094

1.33

(0.93, 1.90)

0.118

No

1.30

0.188

2.02

0.004

1.54

(1.14, 2.09)

0.005

APOE

N/A

e4 Carrier

N/A

Yes

1.74

0.114

1.34

0.318

1.49

(0.96, 2.31)

0.075

No

1.79

0.024

1.91

0.018

1.84

(1.28, 2.66)

0.001

  1. Adjusted effects of single nucleotide variants (SNV) on hippocampal sclerosis (HS). A separate regression model was fit for each variant, mode of inheritance (MOI), and limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) adjustment. All models also adjust for sex, age at death, first three principal components and cohort/study. For rs1990622, rs7781670, and rs704178, the effect alleles are the risk-associated alleles and not the minor alleles. NACC = National Alzheimer's Coordinating Center; ROSMAP = Religious Orders Study and Rush Memory and Aging Project; MOI = mode of inheritance; SNV = single-nucleotide variant; LATE-NC = limbic-predominant age-related TDP-43 encephalopathy neuropathological change; OR = odds ratio; CI = confidence interval.