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Central Institute of Mental Health, Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Central Institute of Mental Health, Clinic of Psychosomatic and Psychotherapeutic Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Transl Psychiatry. 2017 Jun 20;7(6):e1155. doi: 10.1038/tp.2017.115.
Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10) and PKP4 (P=8.67 × 10); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, P=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (r=0.28 [P=2.99 × 10]), SCZ (r=0.34 [P=4.37 × 10]) and MDD (r=0.57 [P=1.04 × 10]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.
边缘型人格障碍（BOR）由环境和遗传因素决定，其特征为情感不稳定和冲动，双相情感障碍（BIP）躁狂发作阶段也有这些诊断症状。高达20%的BIP患者同时患有BOR。本报告描述了在全球最大的BOR患者样本之一中进行的首例BOR病例对照全基因组关联研究（GWAS）。我们分析的重点是：（i）检测与BOR相关的基因和基因集；（ii）研究与BIP的遗传重叠。由于BIP、重度抑郁症（MDD）和精神分裂症（SCZ）之间存在相当大的遗传重叠，且BOR与MDD的共病率很高，我们还分析了BOR与SCZ和MDD的遗传重叠。对998例BOR患者和1545名对照进行了GWAS、基于基因的检测和基因集分析。使用连锁不平衡评分回归来检测BOR与这些疾病之间的遗传重叠。单标记分析在多重检验校正后未发现显著关联。基于基因的分析产生了两个显著基因：DPYD（P = 4.42×10）和PKP4（P = 8.67×10）；基因集分析得出了关于胞吐作用的显著结果（GO:0006887，P = 0.019；FDR，错误发现率）。先前的研究已表明DPYD、PKP4和胞吐作用与BIP和SCZ有关。本研究最显著的发现是BOR与BIP（r = 0.28 [P = 2.99×10]）、SCZ（r = 0.34 [P = 4.37×10]）和MDD（r = 0.57 [P = 1.04×10]）的遗传重叠。我们认为我们的研究首次证明BOR在遗传水平上与BIP、MDD和SCZ重叠。这是否局限于跨诊断临床症状应在未来研究中进行检验。
