Epigenetic prediction of complex traits and death

Table 3 Cox proportional hazards survival models output for phenotypic, epigenetic (DNAm), and genetic (polygenic) predictors of health and lifestyle factors, conditioned on the smoking DNAm score

Trait	Predictor	HR	95% CI	P
Alcohol	Phenotypic	0.95	0.83–1.09	0.457
	Epigenetic	1.11	0.97–1.28	0.134
	Genetic	1.02	0.90–1.17	0.27
	Smoking DNAm	1.46	1.29–1.65	1.4 × 10⁻⁹
Education	Phenotypic	0.93	0.81–1.08	0.352
	Epigenetic	1.00	0.85–1.17	0.979
	Genetic	0.95	0.82–1.10	0.474
	Smoking DNAm	1.48	1.29–1.70	1.8 × 10⁻⁸
BMI	Phenotypic	1.23	1.06–1.42	0.005
	Epigenetic	1.04	0.90–1.20	0.614
	Genetic	1.09	0.94–1.26	0.263
	Smoking DNAm	1.57	1.39–1.78	8.3 × 10⁻¹³
Total cholesterol	Phenotypic	0.85	0.73–0.99	0.031
	Epigenetic	0.95	0.81–1.12	0.542
	Genetic	1.11	0.96–1.27	0.155
	Smoking DNAm	1.49	1.32–1.68	9.7 × 10⁻¹¹
HDL cholesterol	Phenotypic	0.92	0.77–1.09	0.318
	Epigenetic	0.92	0.78–1.08	0.307
	Genetic	1.08	0.94–1.25	0.277
	Smoking DNAm	1.48	1.31–1.67	3.0 × 10⁻¹⁰
LDL with remnant cholesterol	Phenotypic	0.89	0.77–1.03	0.122
	Epigenetic	0.99	0.84–1.17	0.910
	Genetic	1.08	0.93–1.25	0.303
	Smoking DNAm	1.49	1.31–1.68	3.3 × 10⁻¹⁰
Total:HDL cholesterol ratio	Phenotypic	0.99	0.85–1.15	0.870
	Epigenetic	1.12	0.95–1.30	0.170
	Smoking DNAm	1.48	1.30–1.67	6.9 × 10⁻¹⁰
Waist-to-hip ratio	Epigenetic	1.20	1.04–1.39	0.012
	Genetic	0.94	0.82–1.07	0.361
	Smoking DNAm	1.47	1.31–1.66	1.3 × 10⁻¹⁰
Body fat percentage	Epigenetic	1.11	0.96–1.27	0.147
	Genetic	1.19	1.04–1.36	0.013
	Smoking DNAm	1.51	1.34–1.70	1.1 × 10⁻¹¹

Cox proportional hazards outputs are presented for models adjusting for age, sex, phenotypes (where applicable), polygenic scores (where applicable), white blood cell counts, and smoking DNAm scores. All effect sizes are per standard deviation

ISSN: 1474-760X