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

Table 3 Association of 10 IR-associated peripheral blood DNA methylation markers with neurological traits in the Framingham Heart Study

A. all-cause and Alzheimer's dementia
				All-cause dementia			Alzheimer’s dementia
CpG marker	Chr	b37 Position	Closest Gene (bp distance)	B	SE	P	B	SE	P
cg17901584	1	55,353,706	DHCR24 (785)	− 0.0016	0.002	0.43	− 0.0039	0.002	0.09
cg15150970	2	25,473,529	DNMT3A (0)	− 0.0020	0.001	0.12	− 0.0038	0.001	0.007
cg22948094	3	41,172,376	CTNNB1 (64,025)	0.0019	0.002	0.43	0.0025	0.003	0.36
cg12729894	11	1,774,378	MOB2/CTSD (0)	− 0.0025	0.002	0.15	− 0.0052	0.002	0.007
cg27640302	11	57,296,133	TIMM10 (0)	− 0.0005	0.001	0.62	0.0001	0.001	0.92
cg00574958	11	68,607,622	CPT1A (0)	0.0011	0.001	0.27	0.0014	0.001	0.23
cg17058475	11	68,607,737	CPT1A (0)	0.0021	0.001	0.07	0.0023	0.001	0.07
cg24590708	15	52,554,357	MYO5C (0)	− 0.0024	0.003	0.42	− 0.0049	0.003	0.14
cg11024682	17	17,730,094	SREBF1 (0)	− 0.0019	0.001	0.07	− 0.0021	0.001	0.07
cg06500161	21	43,656,587	ABCG1 (0)	− 0.0021	0.001	0.09	− 0.0027	0.001	0.05

B. Brain volumes
				Hippocampal volume			Total brain volume			Log lateral ventricular volume
CpG marker	Chr	b37 Position	Closest Gene (bp distance)	B	SE	P	B	SE	P	B	SE	P
cg17901584	1	55,353,706	DHCR24 (785)	− 0.515	0.943	0.58	− 0.021	0.020	0.28	0.0007	0.0010	0.49
cg15150970	2	25,473,529	DNMT3A (0)	0.903	0.626	0.15	0.021	0.013	0.10	− 0.0013	0.0007	0.06
cg22948094	3	41,172,376	CTNNB1 (64,025)	− 1.511	1.029	0.14	− 0.012	0.022	0.57	− 0.0014	0.0011	0.21
cg12729894	11	1,774,378	MOB2/CTSD (0)	0.793	0.736	0.28	0.023	0.016	0.14	− 0.0013	0.0008	0.10
cg27640302	11	57,296,133	TIMM10 (0)	0.369	0.486	0.45	0.012	0.010	0.24	− 0.0002	0.0005	0.68
cg00574958	11	68,607,622	CPT1A (0)	− 0.142	0.428	0.74	0.020	0.009	0.03	− 0.0008	0.0005	0.07
cg17058475	11	68,607,737	CPT1A (0)	0.291	0.553	0.60	0.038	0.011	*9.7 × 10*⁻⁴	− 0.0013	0.0006	0.03
cg24590708	15	52,554,357	MYO5C (0)	0.646	1.330	0.63	0.007	0.028	0.81	− 0.0004	0.0015	0.78
cg11024682	17	17,730,094	SREBF1 (0)	0.095	0.445	0.83	0.002	0.009	0.79	− 0.0007	0.0005	0.14
cg06500161	21	43,656,587	ABCG1 (0)	0.786	0.549	0.15	0.002	0.012	0.83	− 0.0002	0.0006	0.72

Insulin resistance (IR)
P values in bold and italic passed the multiple-testing significance threshold (P < 0.001)
Linear mixed-effects models were used to evaluate association of dementia risk (all-cause dementia or Alzheimer’s disease dementia, N = 2175) or brain MRI volumes (N = 2279) with blood DNA methylation (outcome) while adjusting for difference between age at survival or age at MRI, respectively, with age at DNA methylation measurement, sex, and blood cell counts

ISSN: 1868-7083