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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.

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Acknowledgements

NESDA: the infrastructure for the NESDA study (www.nesda.nl) is funded through the Geestkracht program of the Netherlands Organisation for Health Research and Development (ZonMw, grant number 10-000-1002) and is supported by participating universities and mental health-care organizations (VU University Medical Center, GGZinGeest, Arkin, Leiden University Medical Center, GGZ Rivierduinen, University Medical Center Groningen, Lentis, GGZ Friesland, GGZ Drenthe, IQ Healthcare, the Netherlands Institute for Health Services Research (NIVEL) and Netherlands Institute of Mental Health and Addiction (Trimbos). NTR (www.tweelingenregister.org): phenotype and sample collection was supported by the European Research Council (ERC Advanced Grant 230374 PI Boomsma), Netherlands Organization for Scientific Research (NWO: MagW/ZonMW grants 904-61-090, 985-10-002, 904-61-193, 480-04-004, 400-05-717, Addiction-31160008 Middelgroot-911-09-032, Spinozapremie 56-464-14192), Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024). Genotyping in NESDA and NTR was supported by Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007), the VU University’s Institute for Health and Care Research (EMGO+), Neuroscience Campus Amsterdam (NCA), the European Community’s Seventh Framework Program (FP7/2007–2013), ENGAGE (HEALTH-F4-2007-201413), Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA), Genetic Association Information Network (GAIN) of the Foundation for the US National Institutes of Health, and the US National Institutes of Mental Health (NIMH, MH081802, 1RC2MH089951-01 PI Sullivan, 1RC2 MH089995-01 PI Hudziak). ERF: the study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007–2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the program ‘Quality of Life and Management of the Living Resources’ of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of data was supported by joint grant from the Netherlands Organisation for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). We thank general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, J Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. We are grateful to all study participants.

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Lubke, G., Laurin, C., Amin, N. et al. Genome-wide analyses of borderline personality features. Mol Psychiatry 19, 923–929 (2014). https://doi.org/10.1038/mp.2013.109

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Keywords

  • borderline personality disorder
  • GCTA
  • GWAS
  • heterogeneity
  • PAI-BOR

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