학술논문
Complex trait methylation scores in the prediction of major depressive disorder
Document Type
article
Author
Miruna C. Barbu; Carmen Amador; Alex S.F. Kwong; Xueyi Shen; Mark J. Adams; David M. Howard; Rosie M. Walker; Stewart W. Morris; Josine L. Min; Chunyu Liu; Jenny van Dongen; Mohsen Ghanbari; Caroline Relton; David J. Porteous; Archie Campbell; Kathryn L. Evans; Heather C. Whalley; Andrew M. McIntosh
Source
EBioMedicine, Vol 79, Iss , Pp 104000- (2022)
Subject
Language
English
ISSN
2352-3964
Abstract
Summary: Background: DNA methylation (DNAm) is associated with time-varying environmental factors that contribute to major depressive disorder (MDD) risk. We sought to test whether DNAm signatures of lifestyle and biochemical factors were associated with MDD to reveal dynamic biomarkers of MDD risk that may be amenable to lifestyle interventions. Methods: Here, we calculated methylation scores (MS) at multiple p-value thresholds for lifestyle (BMI, smoking, alcohol consumption, and educational attainment) and biochemical (high-density lipoprotein (HDL) and total cholesterol) factors in Generation Scotland (GS) (N=9,502) and in a replication cohort (ALSPACadults, N=565), using CpG sites reported in previous well-powered methylome-wide association studies. We also compared their predictive accuracy for MDD to a MDD MS in an independent GS sub-sample (N=4,432). Findings: Each trait MS was significantly associated with its corresponding phenotype in GS (βrange=0.089–1.457) and in ALSPAC (βrange=0.078–2.533). Each MS was also significantly associated with MDD before and after adjustment for its corresponding phenotype in GS (βrange=0.053–0.145). After accounting for relevant lifestyle factors, MS for educational attainment (β=0.094) and alcohol consumption (MSp-value