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 4 Adjusted limbic predominant age-related TDP-43 encephalopathy neuropathological changes (LATE-NC) odds ratios for risk variants

Gene	MOI	SNV	Effect Allele	NACC		ROSMAP		Meta-Analysis
Gene	MOI	SNV	Effect Allele	OR	P-value	OR	P-value	OR	95% CI	P-value
TMEM106B	Additive	rs1990622	A	1.39	0.051	1.08	0.484	1.16	(0.97, 1.39)	0.099
TMEM106B	Additive	rs7781670	C	1.47	0.024	1.09	0.415	1.19	(1.00, 1.43)	0.057
GRN	Additive	rs5848	T	1.40	0.042	1.23	0.089	1.29	(1.06, 1.56)	0.010
ABCC9	Additive	rs1914361	G	1.16	0.354	1.16	0.171	1.16	(0.97, 1.39)	0.098
ABCC9	Recessive	rs1914361	G	0.98	0.933	1.40	0.077	1.25	(0.92, 1.71)	0.151
ABCC9	Additive	rs704178	G	0.95	0.764	1.07	0.536	1.03	(0.86, 1.24)	0.732
ABCC9	Recessive	rs704178	G	0.80	0.433	1.16	0.394	1.05	(0.78, 1.40)	0.759
APOE	Additive	rs769449	A	1.70	0.004	2.22	< 0.001	1.95	(1.51, 2.52)	< 0.001
APOE	N/A	e4 Carrier	N/A	1.88	0.010	2.16	< 0.001	2.05	(1.54, 2.74)	< 0.001

Adjusted effects of single nucleotide variants (SNV) on limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC). All models 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; OR = odds ratio; CI = confidence interval.

ISSN: 2051-5960