Unknown

Dataset Information

0

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

ABSTRACT: 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 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=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 (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). 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.

SUBMITTER: Witt SH 

PROVIDER: S-EPMC5537640 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Genome-wide association study of borderline personality disorder reveals genetic overlap with bipolar disorder, major depression and schizophrenia.

Witt S H SH   Streit F F   Jungkunz M M   Frank J J   Awasthi S S   Reinbold C S CS   Treutlein J J   Degenhardt F F   Forstner A J AJ   Heilmann-Heimbach S S   Dietl L L   Schwarze C E CE   Schendel D D   Strohmaier J J   Abdellaoui A A   Adolfsson R R   Air T M TM   Akil H H   Alda M M   Alliey-Rodriguez N N   Andreassen O A OA   Babadjanova G G   Bass N J NJ   Bauer M M   Baune B T BT   Bellivier F F   Bergen S S   Bethell A A   Biernacka J M JM   Blackwood D H R DHR   Boks M P MP   Boomsma D I DI   Børglum A D AD   Borrmann-Hassenbach M M   Brennan P P   Budde M M   Buttenschøn H N HN   Byrne E M EM   Cervantes P P   Clarke T-K TK   Craddock N N   Cruceanu C C   Curtis D D   Czerski P M PM   Dannlowski U U   Davis T T   de Geus E J C EJC   Di Florio A A   Djurovic S S   Domenici E E   Edenberg H J HJ   Etain B B   Fischer S B SB   Forty L L   Fraser C C   Frye M A MA   Fullerton J M JM   Gade K K   Gershon E S ES   Giegling I I   Gordon S D SD   Gordon-Smith K K   Grabe H J HJ   Green E K EK   Greenwood T A TA   Grigoroiu-Serbanescu M M   Guzman-Parra J J   Hall L S LS   Hamshere M M   Hauser J J   Hautzinger M M   Heilbronner U U   Herms S S   Hitturlingappa S S   Hoffmann P P   Holmans P P   Hottenga J-J JJ   Jamain S S   Jones I I   Jones L A LA   Juréus A A   Kahn R S RS   Kammerer-Ciernioch J J   Kirov G G   Kittel-Schneider S S   Kloiber S S   Knott S V SV   Kogevinas M M   Landén M M   Leber M M   Leboyer M M   Li Q S QS   Lissowska J J   Lucae S S   Martin N G NG   Mayoral-Cleries F F   McElroy S L SL   McIntosh A M AM   McKay J D JD   McQuillin A A   Medland S E SE   Middeldorp C M CM   Milaneschi Y Y   Mitchell P B PB   Montgomery G W GW   Morken G G   Mors O O   Mühleisen T W TW   Müller-Myhsok B B   Myers R M RM   Nievergelt C M CM   Nurnberger J I JI   O'Donovan M C MC   Loohuis L M O LMO   Ophoff R R   Oruc L L   Owen M J MJ   Paciga S A SA   Penninx B W J H BWJH   Perry A A   Pfennig A A   Potash J B JB   Preisig M M   Reif A A   Rivas F F   Rouleau G A GA   Schofield P R PR   Schulze T G TG   Schwarz M M   Scott L L   Sinnamon G C B GCB   Stahl E A EA   Strauss J J   Turecki G G   Van der Auwera S S   Vedder H H   Vincent J B JB   Willemsen G G   Witt C C CC   Wray N R NR   Xi H S HS   Tadic A A   Dahmen N N   Schott B H BH   Cichon S S   Nöthen M M MM   Ripke S S   Mobascher A A   Rujescu D D   Lieb K K   Roepke S S   Schmahl C C   Bohus M M   Rietschel M M  

Translational psychiatry 20170620 6

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 inv  ...[more]

Similar Datasets

Unknown Analysis of genome-wide significant bipolar disorder genes in borderline personality disorder.
| S-EPMC4219535 | biostudies-literature
Unknown Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence.
| S-EPMC6609490 | biostudies-literature
Unknown Molecular genetic overlap in bipolar disorder, schizophrenia, and major depressive disorder.
| S-EPMC3406228 | biostudies-literature
Unknown The overlap between autistic spectrum conditions and borderline personality disorder.
| S-EPMC5590952 | biostudies-literature
Unknown Circadian rest-activity patterns in bipolar disorder and borderline personality disorder.
| S-EPMC6702232 | biostudies-literature
Unknown Desynchronization of diurnal rhythms in bipolar disorder and borderline personality disorder.
| S-EPMC5895697 | biostudies-literature
Unknown Self-report screening instruments differentiate bipolar disorder and borderline personality disorder.
| S-EPMC8323027 | biostudies-literature
Unknown The genetic association between personality and major depression or bipolar disorder. A polygenic score analysis using genome-wide association data.
| S-EPMC3309491 | biostudies-literature
Unknown Borderline personality disorder.
| S-EPMC558173 | biostudies-literature
Unknown Daily longitudinal self-monitoring of mood variability in bipolar disorder and borderline personality disorder.
| S-EPMC5296237 | biostudies-literature