Genome-wide association study of borderline personality disorder identifies 11 loci and highlights shared risk with mental and somatic disorders.

Identifier:  imarina:9464376

Handle: https://hdl.handle.net/20.500.11797/imarina9464376

Authors:  Streit F; Awasthi S; Hall AS; Braun A; Niarchou M; Marouli E; Babajide O; Frank J; Zillich L; Callies CM; Avetyan D; Zillich E; Naamanka J; Gonzalez J; Harder A; Lu Y; Aherrahrou Z; Ahmad ZU; Ask H; Batzler A; Benros ME; Brand-de Wilde OM; Brunak S; Bruun MT; Christoffersen LA; Colodro-Conde L; Coombes BJ; Corfield EC; Dahmen N; Didriksen M; Dinh KM; Djurovic S; Dowsett J; Drange OK; Dukal H; Edelmann S; Erikstrup C; Espinola MK; Fassbinder E; Faucon A; de Sá DSF; Foo JC; Gilles M; Gutiérrez-Zotes A; Hansen TF; Haraldsson M; Harper RP; Havdahl A; Heilbronner U; Herms S; Hjalgrim H; Hübel C; Jacob GA; Aagaard B; Jorgensen A; Jungkunz M; Kleindienst N; Knoblich N; Koglin S; Kraft J; Krebs K; Lee CW; Lin Y; Lis S; Lisoway A; Malogiannis IA; Martinsen A; Maslahati T; Merz K; Meyer-Lindenberg A; Mikkelsen S; Mikkelsen C; Mobascher A; Muntané G; Oddsson A; Ostrowski SR; Palviainen T; Pedersen OB; Pedersen G; Quinn L; Reinhard MA; Ruths FA; Schott BH; Schredl M; Schwarz E; Schwarze CE; Schwinn M; Send T; Sigurdsson E; Simon-Keller K; Skuladottir AT; Soler J; Sonley A; Sørensen E; Stefansson H; Straub P; Suvisaari J; Tesli M; Træholt J; Ullum H; Völker MP; Walters GB; Wang R; Witt CC; Zarbock G; Zill P; Zwart JA; Andreassen OA; Arntz A; Biernacka JM; Bohus M; Breen G; Chapman AL; Cichon S; Davis LK; Deuschle M; Euler S; Herpertz SC; Hummelen B; Jobst A; Kaprio J; Kennedy JL; Lehto K; Lieb K; Martorell L; McMain S; Musil R; Nieratschker V; Nöthen MM; Padberg F; Palotie A; Pascual JC; Perroud N; Ramos-Quiroga JA; Reichborn-Kjennerud T; Ribases M; Roepke S; Rujescu D; Sanchez-Roige S; Schilling C; Schmahl C; Stefansson K; Thorgeirsson TE; Turecki G; Vilella E; Werge T; Winsvold BS; Wrege J; Rietschel M; Ripke S; Witt SH

Abstract:
We conducted the largest genome-wide meta-analysis of borderline personality disorder (BPD) to date, with a discovery sample of 12,339 cases and 1,041,717 controls, and a replication study of 685 cases and 107,750 controls (all participants of European ancestry). We identified 11 independent associated genomic loci, and nine risk genes in the gene-based analysis. We observed a single-nucleotide polymorphism (SNP) heritability of 17.3% and derived polygenic scores (PGS) predicted 4.6% of the phenotypic variance in BPD on the liability scale. BPD showed the strongest positive genetic correlations with GWAS of posttraumatic stress disorder, depression, attention deficit hyperactivity disorder, antisocial behavior, and measures of suicide and self-harm. Phenome-wide association analyses using BPD-PGS confirmed these associations and additionally revealed associations with general medical conditions including obstructive pulmonary disease and diabetes. The present analyses highlight BPD as a polygenic disorder, with the genetic risk showing substantial overlap with psychiatric and physical health conditions.