Borderline personality disorder and childhood maltreatment: a genome‐wide methylation analysis

<jats:p>Early life adversity plays a critical role in the emergence of borderline personality disorder (<jats:styled-content style="fixed-case">BPD</jats:styled-content>) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole‐genome methylation scan of <jats:styled-content style="fixed-case">BPD</jats:styled-content> subjects. Using the Illumina Infinium® <jats:styled-content style="fixed-case">HumanMethylation450 BeadChip</jats:styled-content>, global methylation status of <jats:styled-content style="fixed-case">DNA</jats:styled-content> extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 <jats:styled-content style="fixed-case">BPD</jats:styled-content> subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (<jats:styled-content style="fixed-case">MDD</jats:styled-content>) and reporting a low rate of child maltreatment. Several <jats:styled-content style="fixed-case">CpGs</jats:styled-content> within or near the following genes <jats:italic>(<jats:styled-content style="fixed-case">IL17RA</jats:styled-content>, <jats:styled-content style="fixed-case">miR124‐3</jats:styled-content>, <jats:styled-content style="fixed-case">KCNQ2</jats:styled-content>, <jats:styled-content style="fixed-case">EFNB1</jats:styled-content>, <jats:styled-content style="fixed-case">OCA2</jats:styled-content></jats:italic>, <jats:italic><jats:styled-content style="fixed-case">MFAP2</jats:styled-content>, <jats:styled-content style="fixed-case">RPH3AL</jats:styled-content>, <jats:styled-content style="fixed-case">WDR60</jats:styled-content>, <jats:styled-content style="fixed-case">CST9L</jats:styled-content></jats:italic>, <jats:italic><jats:styled-content style="fixed-case">EP400</jats:styled-content></jats:italic>, <jats:italic><jats:styled-content style="fixed-case">A2ML1</jats:styled-content></jats:italic>, <jats:italic><jats:styled-content style="fixed-case">NT5DC2</jats:styled-content>, <jats:styled-content style="fixed-case">FAM163A</jats:styled-content> and <jats:styled-content style="fixed-case">SPSB2</jats:styled-content>)</jats:italic> were found to be differently methylated, either in <jats:styled-content style="fixed-case">BPD</jats:styled-content> compared with <jats:styled-content style="fixed-case">MDD</jats:styled-content> or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to <jats:italic><jats:styled-content style="fixed-case">miR124‐3</jats:styled-content></jats:italic> that was significantly associated with <jats:styled-content style="fixed-case">BPD</jats:styled-content> and severity of childhood maltreatment. <jats:italic><jats:styled-content style="fixed-case">miR124‐3</jats:styled-content></jats:italic> codes for a <jats:styled-content style="fixed-case">microRNA</jats:styled-content> (<jats:styled-content style="fixed-case">miRNA</jats:styled-content>) targeting several genes previously found to be associated with <jats:styled-content style="fixed-case">BPD</jats:styled-content> such as <jats:italic><jats:styled-content style="fixed-case">NR3C1</jats:styled-content></jats:italic>. Our results highlight the potentially important role played by <jats:styled-content style="fixed-case">miRNAs</jats:styled-content> in the etiology of neuropsychiatric disorders such as <jats:styled-content style="fixed-case">BPD</jats:styled-content> and the usefulness of using methylome‐wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.</jats:p>