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

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

Gene	MOI	SNV	Effect Allele	LATE-NC Adjusted	NACC		ROSMAP		Meta-Analysis
Gene	MOI	SNV	Effect Allele	LATE-NC Adjusted	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
TMEM106B	Additive	rs1990622	A	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
TMEM106B	Additive	rs7781670	C	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
GRN	Additive	rs5848	T	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
ABCC9	Additive	rs1914361	G	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
ABCC9	Recessive	rs1914361	G	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
ABCC9	Additive	rs704178	G	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
ABCC9	Recessive	rs704178	G	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
APOE	Additive	rs769449	A	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
APOE	N/A	e4 Carrier	N/A	No	1.79	0.024	1.91	0.018	1.84	(1.28, 2.66)	0.001

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.

ISSN: 2051-5960