Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20

Jessica Ross; Wade Berrettini; William Coryell; Elliot S Gershon; Judith A Badner; John R Kelsoe; Melvin G McInnis; Francis J McMahon; Dennis L Murphy; John I Nurnberger; Tatiana Foroud; John P Rice; William B Scheftner; Peter Zandi; Howard Edenberg; William Byerley

doi:10.1097/YPG.0b013e3283050aa5

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Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20

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Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20

Jessica Ross, Wade Berrettini, William Coryell, Elliot S Gershon, Judith A Badner, John R Kelsoe, Melvin G McInnis, Francis J McMahon, Dennis L Murphy, John I Nurnberger, …

Psychiatric genetics, Vol.18(4), pp.191-198

08/2008

DOI: 10.1097/YPG.0b013e3283050aa5

PMCID: PMC4418612

PMID: 18628681

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Abstract

Objective: Our aim is to map chromosomal regions that harbor loci that increase susceptibility to bipolar disorder. Methods: We analyzed 644 bipolar families ascertained by the National Institute of Mental Health Human Genetics Initiative for bipolar disorder. The families have been genotyped with microsatellite loci spaced every approximately 10 cM or less across the genome. Earlier analyses of these pedigrees have been limited to nonparametric (model-free) methods and thus, information from unaffected subjects with genotypes was not considered. In this study, we used parametric analyses assuming dominant and recessive transmission and specifying a maximum penetrance of 70%, so that information from unaffecteds could be weighed in the linkage analyses. As in previous linkage analyses of these pedigrees, we analyzed three diagnostic categories: model 1 included only bipolar I and schizoaffective, bipolar cases (1565 patients of whom approximately 4% were schizoaffective, bipolar); model 2 included all individuals in model 1 plus bipolar II patients (1764 total individuals); and model 3 included all individuals in model 2 with the addition of patients with recurrent major depressive disorder (2046 total persons). Results: Assuming dominant inheritance the highest genome-wide pair-wise logarithm of the odds (LOD) score was 3.2 with D16S749 using model 2 patients. Multipoint analyses of this region yielded a maximum LOD score of 4.91. Under recessive transmission a number of chromosome 20 markers were positive and multipoint analyses of the area gave a maximum LOD of 3.0 with model 2 cases. Conclusion: The chromosome 16p and 20 regions have been implicated by some studies and the data reported herein provide additional suggestive evidence of bipolar susceptibility genes in these regions.

Gene Mapping

Genetics

bipolar disorder

linkage analysis

chromosome 20

complex disorder

parametric analysis

chromosome 16

Details

Title: Subtitle: Genome-wide parametric linkage analyses of 644 bipolar pedigrees suggest susceptibility loci at chromosomes 16 and 20
Creators: Jessica Ross - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Wade Berrettini - Department of Psychiatry, Johns Hopkins University, Maryland, USA
William Coryell - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Elliot S Gershon - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Judith A Badner - Department of Psychiatry, Johns Hopkins University, Maryland, USA
John R Kelsoe - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Melvin G McInnis - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Francis J McMahon - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Dennis L Murphy - Department of Psychiatry, Johns Hopkins University, Maryland, USA
John I Nurnberger - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Tatiana Foroud - Department of Psychiatry, Johns Hopkins University, Maryland, USA
John P Rice - Department of Psychiatry, Johns Hopkins University, Maryland, USA
William B Scheftner - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Peter Zandi - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Howard Edenberg - Department of Psychiatry, Johns Hopkins University, Maryland, USA
William Byerley - Department of Psychiatry, Johns Hopkins University, Maryland, USA
Resource Type: Journal article
Publication Details: Psychiatric genetics, Vol.18(4), pp.191-198
DOI: 10.1097/YPG.0b013e3283050aa5
PMID: 18628681
PMCID: PMC4418612
NLM abbreviation: Psychiatr Genet
ISSN: 0955-8829
eISSN: 1473-5873
Language: English
Date published: 08/2008
Academic Unit: Psychiatry
Record Identifier: 9984003419802771

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