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Correspondence: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, One Gustave L. Levy Place, New York 10029, NY, USA. E-mail: pamela.sklar@mssm.edu

We are grateful for the participation of all subjects contributing to this research, and to the collection team that worked to recruit them.

The funders had no role in study design, execution, analysis or manuscript preparation.

The authors declare no conflict of interest.

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Research Funding:

We acknowledge funding support from National Institutes of Health (NIH)/National Institute of Mental Health (NIMH) grant R01MH085542 (AWC, JWS and PS), NIH/NIMH grant R01MH085545 (JWS), NIH/NIMH grant R01MH085548 (AHF, CNP, CPM, DM, DOP, DSL, ELB, HM, HN, JAK, JJR, JLS, LJF, MAE, MHR, MTP, PFB and SRM), NIH/NIMH grant K99MH101367 (PHL), the Stanley Medical Research Institute (JLM, KC, RAB and SAM), philanthropic gifts from Kent and Elizabeth Dauten and Ted and Vada Stanley (JLM, KC, RAB and SAM), the Swedish Research Council 2013-3196 (CMH), the Swedish Medical Research Council grants K2014-62X-14647-12-51 and K2010-61 P-21568-01-4 (ML), the Swedish foundation for Strategic Research grant KF10-0039 (ML), the Swedish Federal Government under the LUA/ALF agreement grants ALF 20130032 and ALFGBG-142041 (ML), European Commission-Marie Curie Fellowship (AD), Wellcome Trust (IJ, KG, LAJ, LF and NC).

Work at the Icahn School of Medicine at Mount Sinai was also supported by the Institute for Genomics and Multiscale Biology (including computational resources and staff expertise provided by the Department of Scientific Computing).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Psychiatry
  • GENOME-WIDE ASSOCIATION
  • SPECTRUM DISORDER
  • II DISORDER
  • RISK LOCI
  • SCHIZOPHRENIA
  • FAMILY
  • DEPRESSION
  • UNIPOLAR
  • ILLNESS
  • SUSCEPTIBILITY

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder

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Journal Title:

Translational Psychiatry

Volume:

Volume 7, Number 1

Publisher:

, Pages e993-e993

Type of Work:

Article | Final Publisher PDF

Abstract:

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10(-8)) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h(2)=0.35; BD II SNP-h(2)=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

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© 2017 The Author(s)

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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