Multi-tissue epigenetic analysis identifies distinct associations underlying insulin resistance and Alzheimer’s disease at CPT1A locus

Table 4 Association of 10 IR-associated peripheral blood DNA methylation markers with neurological traits in ROSMAP

CpG marker	Closest Gene (bp distance)	Clinical diagnosis of cognitive status at time of death			Braak stage			CERAD score
CpG marker	Closest Gene (bp distance)	B	SE	P	B	SE	P	B	SE	P
cg17901584	DHCR24 (785)	− 0.0006	0.0009	0.50	0.0006	0.0012	0.60	0.0014	0.0012	0.25
cg15150970	DNMT3A (0)	0.0008	0.0007	0.25	0.0002	0.0008	0.78	0.0004	0.0009	0.63
cg22948094	CTNNB1 (64,025)	0.0023	0.0010	0.02	0.0014	0.0012	0.27	− 0.0017	0.0013	0.17
cg12729894	MOB2/CTSD (0)	− 0.0007	0.0005	0.14	− 0.0001	0.0006	0.92	0.0008	0.0006	0.23
cg27640302	TIMM10 (0)	0.0007	0.0006	0.29	0.0004	0.0008	0.62	− 0.0004	0.0008	0.63
cg00574958	CPT1A (0)	0.0013	0.0004	0.005	0.0016	0.0006	0.004	− 0.0020	0.0006	*0.0005*
cg17058475	CPT1A (0)	0.0012	0.0005	0.02	0.0016	0.0006	0.01	− 0.0021	0.0007	*0.001*
cg24590708	MYO5C (0)	0.0011	0.0017	0.52	− 0.0003	0.0022	0.88	0.0015	0.0022	0.50
cg11024682	SREBF1 (0)	− 0.0002	0.0006	0.79	− 0.0002	0.0008	0.79	0.0002	0.0008	0.79
cg06500161	ABCG1 (0)	− 0.0007	0.0006	0.27	3.6 × 10^–5	0.0008	0.96	0.0013	0.0008	0.10

ROSMAP Religious Orders Study (ROS) and Memory and Aging Project (MAP)
Clinical diagnosis of cognitive status at time of death (6 other dementia, 5 Possible Alzheimer’s dementia (AD), 4 Probable AD, 3 mild cognitive impairment [MCI] and another condition, 2 MCI and no other condition, 1 no cognitive impairment), Braak stage: measure of severity of neurofibrillary tangle pathology (coded 0, I to VI), CERAD score: neuropathologic diagnosis based on estimates of neuritic plaque density (1 definite AD, 2 probable, 3 possible, 4 no AD)
P values in bold and italic passed the multiple-testing significance threshold (P < 0.002)
Linear regression models were used to evaluate association of brain DNA methylation (outcome) with clinical cognitive diagnosis or AD-related indices (N = 707), adjusting for age at death, sex, substudy, self-reported race, batch, and cell type proportions

ISSN: 1868-7083