Figure 2. Four developmental profiles for cortical DNA methylation.

(A) Associations of log-transformed PMR values (ln(PMR+1); y-axis) with age (x-axis) for several representative genes. Trends are studied using linear regression. HOXA1 shows a linear association. MGMT-M2B shows a non-linear shift, with the P-value referring to a T-test of the difference in mean methylation value for subjects under or over 50 years of age. For the biphasic linear trends of PAX8 and the ALU sequence ALU-M1B (Table S2) , the P-values refer to a test of change of slope. Green dots = controls, blue triangles = schizophrenia and red squares = Alzheimer's subjects. (B) Schematic summary of the four different types (1–4, see text for details) of developmental methylation profiles in human temporal cortex across the lifespan (x-axis, B = birth), as illustrated by the representative examples in (A). (C) Listings and proportion of gene loci (total = 48; excluding AR and FAM127A which showed gender-specific methylation) that show significant age-dependent methylation changes: colors refer to the scheme in (B). Gray sector refers to the subset of loci without a significant age effect. N = 125 subjects. All p-values are adjusted for diagnosis; *** p<0.0001, ** p<0.001, * p<0.05.