A cell epigenotype specific model for the correction of brain cellular heterogeneity bias and its application to age, brain region and major depression.

3 A recent methylome profiling study in major depressive disorder (MDD) did not identify any significant loci after correction for multiple testing; however, it successfully validated 60% of the top nominally significant differences. 4 In the above studies, the brain samples interrogated consisted of “bulk” brain tissue preparations representing cellularly heterogeneous mixes of neuronal and non-neuronal cell types.

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We performed spot-wise t-tests across tissues and observed highly significant FDR corrected differences similar to that of our neuron vs. non-neuron comparison in Figure 1A with FDR p values ranging as low as 3.1 × 10 −126 ( Fig. 5C ).

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