One differentially methylated probe (DMP) (cg00933603 p = 3.54 × 10 −7) in VARS2, a mitochondrial aminoacyl-tRNA synthetase, remained significantly hypomethylated after multiple-testing correction.
We evaluated DNA methylation differences between High-BD-PRS and Low-BD-PRS strata using linear models. The High-BD-PRS stratum also had higher mean cross-disorder-PRS and MDD-PRS (ANCOVA p = 0.035 and p = 0.024, respectively). Unrelated HR participants of European ancestry ( n = 103) were stratified based on their BD-PRS score within the HR-population distribution, and the top two quintiles (High-BD-PRS n = 41) compared against the bottom two quintiles (Low-BD-PRS n = 41). Polygenic risk scores (PRS) were calculated using summary statistics from recent genome-wide association studies for BD, major depressive disorder (MDD) and cross-disorder (meta-analysis of eight psychiatric disorders). Peripheral blood-derived DNA was assayed using Illumina PsychArray, and Methylation-450K or -EPIC BeadChips. We herein sought to identify epigenetic signatures operating in the context of polygenic risk for BD in young people at high familial risk (HR) of BD. Translational Psychiatry volume 12, Article number: 310 ( 2022)Įnvironmental factors contribute to risk of bipolar disorder (BD), but how environmental factors impact the development of psychopathology within the context of elevated genetic risk is unknown. Epigenetic signatures relating to disease-associated genotypic burden in familial risk of bipolar disorder
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