Journal article
Genome Wide Linkage Analysis of 972 Bipolar Pedigrees Using Single Nucleotide Polymorphisms
Molecular psychiatry, Vol.17(8), pp.818-826
07/2012
DOI: 10.1038/mp.2011.89
PMCID: PMC3204161
PMID: 21769101
Abstract
Because of the high costs associated with ascertainment of families most linkage studies of Bipolar I disorder (BPI) have used relatively small samples. Moreover, the genetic information content reported in most studies has been less than 0.6. While microsatellite markers spaced every 10 centimorgans typically extract most of the genetic information content for larger multiplex families, they can be less informative for smaller pedigrees especially for affected sib pair kindreds. For these reasons we collaborated to pool family resources and carry out higher density genotyping. Approximately 1100 pedigrees of European ancestry were initially selected for study and were genotyped by the Center for Inherited Disease Research using the Illumina Linkage Panel 12 set of 6090 SNPs. Of the ~1100 families, 972 were informative for further analyses and mean information content was 0.86 after pruning for LD. The 972 kindreds include 2284 cases of BPI disorder, 498 individuals with Bipolar II disorder (BPII) and 702 subjects with Recurrent Major Depression. Three affection status models were considered: ASM1 (BPI and schizoaffective disorder, BP cases (SABP) only), ASM2 (ASM1 cases plus BPII) and ASM3 (ASM2 cases plus Recurrent Major Depression). Both parametric and non-parametric linkage methods were carried out. The strongest findings occurred at 6q21 (Nonparametric Pairs Lod 3.4 for rs1046943 at 119 cM) and 9q21 (Nonparametric Pairs Lod 3.4 for rs722642 at 78 cM) using only BPI and SA, BP cases. Both results met genome-wide significant criteria, although neither was significant after correction for multiple analyses. We also inspected parametric scores for the larger multiplex families to identify possible rare susceptibility loci. In this analysis we observed 59 parametric lods of 2 or greater, many of which are likely to be close to maximum possible scores. While some linkage findings may be false positives the results could help prioritize the search for rare variants using whole exome or genome sequencing.
Details
- Title: Subtitle
- Genome Wide Linkage Analysis of 972 Bipolar Pedigrees Using Single Nucleotide Polymorphisms
- Creators
- Judith A Badner - Department of Psychiatry, University of Chicago, Chicago, IL USADaniel Koller - Department of Medical and Molecular Genetics, Indiana University School of MedicineTatiana Foroud - Department of Medical and Molecular Genetics, Indiana University School of MedicineHoward Edenberg - Department of Medical and Molecular Genetics, Indiana University School of MedicineJohn I Nurnberger - Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN USAPeter P Zandi - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, MD USAVirginia L Willour - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, MD USAFrancis J McMahon - Unit on the Genetic Basis of Mood and Anxiety Disorders, Mood and Anxiety Disorders Program, National Institute of Mental Health, National Institutes of Health, US Dept of Health and Human Services, Bethesda, MD, USAJames B Potash - Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine and Bloomberg School of Public Health, Baltimore, MD USAMarian Hamshere - MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UKDetelina Grozeva - MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UKElaine Green - MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UKGeorge Kirov - MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UKIan Jones - MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UKLisa Jones - Neuropharmacology & Neurobiology, University of Birmingham, Birmingham, UKNicholas Craddock - MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UKDerek Morris - Trinity College, Dublin, IrelandRicardo Segurado - Trinity College, Dublin, IrelandMike Gill - Trinity College, Dublin, IrelandDessa Sadovnick - Department of Medical Genetics, University of British Columbia, Vancouver, CARonald Remick - Department of Psychiatry, St. Paul's Hospital, Vancouver, CAPaul Keck - Department of Psychiatry, University of Cincinnati, Ohio, USAJohn Kelsoe - Department of Psychiatry, University of California San Diego, La Jolla, CAMuhammad Ayub - School of Medicine and Health, University of Durham, Durham, UKAlan MacLean - Division of Psychiatry, University of Edinburgh, Edinburgh, UKDouglas Blackwood - Division of Psychiatry, University of Edinburgh, Edinburgh, UKChun-Yu Liu - Department of Psychiatry, University of Chicago, Chicago, IL USAElliot S Gershon - Department of Psychiatry, University of Chicago, Chicago, IL USAWilliam McMahon - Department of Psychiatry, University of Utah Medical Center, Salt Lake City, UT USAGholson Lyon - Department of Psychiatry, University of Utah Medical Center, Salt Lake City, UT USAReid Robinson - Department of Psychiatry, University of Utah Medical Center, Salt Lake City, UT USAJessica Ross - Department of Psychiatry, University of California San Francisco, San Francisco CA USAWilliam Byerley - Department of Psychiatry, University of California San Francisco, San Francisco CA USA
- Resource Type
- Journal article
- Publication Details
- Molecular psychiatry, Vol.17(8), pp.818-826
- DOI
- 10.1038/mp.2011.89
- PMID
- 21769101
- PMCID
- PMC3204161
- ISSN
- 1359-4184
- eISSN
- 1476-5578
- Language
- English
- Date published
- 07/2012
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070969902771
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