Twin Study of Early-Onset Major Depression Finds DNA Methylation Enrichment for Neurodevelopmental Genes
Twin Study of Early-Onset Major Depression Finds DNA Methylation Enrichment for Neurodevelopmental Genes
Abstract Major depression (MD) is a debilitating mental health condition with peak prevalence occurring early in life. Genome-wide examination of DNA methylation (DNAm) offers an attractive comple ment to studies of allelic risk given it can reflect the combined influence of genes and environment. The current study used a co-twin control design to identify differentially and variably methylated regions of the genome that distinguish monozygotic (MZ) twins with and without a lifetime history of early-onset MD. The sample included 150 Caucasian monozygotic twins (73% female; Mage=17.52 SD=1.28) assessed during a developmental stage characterized by relatively dis tinct neurophysiological changes. All twins were generally healthy and currently free of medica tions with psychotropic effects. DNAm was measured in peripheral blood cells using the Infinium Human BeadChip 450K Array. MD associations were detected at 760 differentially and variably methylated probes/regions that mapped to 428 genes. Results indicated an association between early-onset MD and many genes and genomic regions involved in neural circuitry formation, pro jection, functioning, and plasticity. Gene enrichment analyses implicated genes related to neuron structures and neurodevelopmental processes including cell-cell adhesion genes (e.g., CDHs, PCDHAs, PCDHA1C/2C). Genes previously implicated in mood and psychiatric disorders as well as chronic stress (e.g., HDAC4, NRG1) also were identified. DNAm regions associated with MD where found to overlap genetic loci observed in the latest Psychiatric Genomics Consortium meta‐ analysis of depression. Understanding the time course of epigenetic influences during emerging adulthood may clarify developmental phases where genes modulate individual differences in MD risk.
Lapato Dana M.、Lancaster Eva E.、Webb Bradley T.、Wolen Aaron R.、Verhulst Bradley、Hettema John M.、York Timothy P.、Roberson-Nay Roxann
Virginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral Genetics||Virginia Commonwealth University, Department of Human and Molecular GeneticsVirginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral Genetics||Virginia Commonwealth University, Department of Human and Molecular GeneticsVirginia Commonwealth University, Department of Psychiatry||Virginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral Genetics||Virginia Commonwealth University, Department of Human and Molecular GeneticsVirginia Commonwealth University, Department of Human and Molecular GeneticsDepartment of Psychology, Michigan State University, East LansingVirginia Commonwealth University, Department of Psychiatry||Virginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral GeneticsVirginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral Genetics||Virginia Commonwealth University, Department of Human and Molecular GeneticsVirginia Commonwealth University, Department of Psychiatry||Virginia Commonwealth University, Virginia Institute for Psychiatric and Behavioral Genetics
神经病学、精神病学基础医学医学研究方法
Lapato Dana M.,Lancaster Eva E.,Webb Bradley T.,Wolen Aaron R.,Verhulst Bradley,Hettema John M.,York Timothy P.,Roberson-Nay Roxann.Twin Study of Early-Onset Major Depression Finds DNA Methylation Enrichment for Neurodevelopmental Genes[EB/OL].(2025-03-28)[2025-04-30].https://www.biorxiv.org/content/10.1101/422345.点此复制
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