title: Genome-wide analyses of borderline personality features.
abstract: The heritability of borderline personality (BP) features has been established in multiple twin and family studies. Using data from the borderline subscale of the Personality Assessment Inventory Borderline Features Scale (PAI-BOR) collected in two Dutch cohorts (N=7125), the Netherlands Twin Register and The Netherlands Study of Depression and Anxiety, we show that heritability of the PAI-BOR total score using genome-wide single-nucleotide polymorphism (SNPs) is estimated at 23%, and that the genetic variance is substantially higher in affect instability items compared with the other three subscales of the PAI-BOR (42.7% vs non-significant estimates for self-harm, negative relations and identity problems). We present results from a first genome-wide association study of BP features, which shows a promising signal on chromosome 5 corresponding to SERINC5, a protein involved in myelination. Reduced myelination has been suggested as possibly having a role in the development of psychiatric disorders characterized by lack of social interaction. The signal was confirmed in a third independent Dutch cohort drawn from the Erasmus Rucphen Family study (N=1301). Our analyses were complemented by investigating the heterogeneity that was implied by the differences in genetic variance components in the four subscales of the PAI-BOR. These analyses show that the association of SNPs tagging SERINC5 differs substantially across the 24 items of the PAI-BOR. Further, using reverse regression we showed that the effects were present only in subjects with higher scores on the PAI-BOR. Taken together, these results suggest that future genome-wide analyses can benefit substantially by taking into account the phenotypic and genetic heterogeneity of BP features.
authors: 1] University of Notre Dame, Notre Dame, IN, USA [2] VU University Amsterdam, Amsterdam, The Netherlands.
authors: G H
authors: GH
authors: Lubke
authors: VU University Amsterdam, Amsterdam, The Netherlands.
authors: C
authors: C
authors: Laurin
authors: Erasmus Medical Center, Rotterdam, The Netherlands.
authors: N
authors: N
authors: Amin
authors: VU University Amsterdam, Amsterdam, The Netherlands.
authors: J J
authors: JJ
authors: Hottenga
authors: VU University Amsterdam, Amsterdam, The Netherlands.
authors: G
authors: G
authors: Willemsen
authors: 1] VU University Medical Center and GGZinGeest, Amsterdam, The Netherlands [2] Centre for Medical Systems Biology, Leiden, The Netherlands.
authors: G
authors: G
authors: van Grootheest
authors: VU University Amsterdam, Amsterdam, The Netherlands.
authors: A
authors: A
authors: Abdellaoui
authors: Erasmus Medical Center, Rotterdam, The Netherlands.
authors: L C
authors: LC
authors: Karssen
authors: Erasmus Medical Center, Rotterdam, The Netherlands.
authors: B A
authors: BA
authors: Oostra
authors: 1] Erasmus Medical Center, Rotterdam, The Netherlands [2] Centre for Medical Systems Biology, Leiden, The Netherlands [3] Netherlands Consortium on Healthy Aging, The Hague, The Netherlands.
authors: C M
authors: CM
authors: van Duijn
authors: 1] VU University Medical Center and GGZinGeest, Amsterdam, The Netherlands [2] Centre for Medical Systems Biology, Leiden, The Netherlands.
authors: B W J H
authors: BW
authors: Penninx
authors: 1] VU University Amsterdam, Amsterdam, The Netherlands [2] Centre for Medical Systems Biology, Leiden, The Netherlands.
authors: D I
authors: DI
authors: Boomsma
mesh_terms: D017677:Age Distribution; D001883:Borderline Personality Disorder / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D008565:Membrane Proteins
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