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. 2008 Aug;18(4):191-8.
doi: 10.1097/YPG.0b013e3283050aa5.

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

Jessica Ross  1 , 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 Jr, Tatiana Foroud, John P Rice, William B Scheftner, Peter Zandi, Howard Edenberg, William Byerley
Affiliations

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

Jessica Ross et al. Psychiatr Genet. 2008 Aug.

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.

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Figures

Fig 1
Fig 1
Chromosome 16 maximum multipoint logarithm of the odds scores using a bipolar II – dominant transmission model.
Fig 2
Fig 2
Chromosome 20 maximum multipoint logarithm of the odds scores using a bipolar II – recessive transmission model.
See this image and copyright information in PMC

References

    1. Abreu PC, Greenberg DA, Hodge SE. Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases. Am J Hum Genet. 1999;65:847–857. - PMC - PubMed
    1. Adams LJ, Mitchell PB, Fielder SL, Rosso A, Donald JA, Schofield PR. A susceptibility locus for bipolar affective disorder on chromosome 4q35. Am J Hum Genet. 1998;62:1084–1091. - PMC - PubMed
    1. Avramopoulos D, Willour VL, Zandi PP, Huo Y, Mackinnon DF, Potash JB, et al. Linkage of bipolar affective disorder on chromosome 8q24: follow-up and parametric analysis. Mol Psychiatry. 2004;9:191–196. - PubMed
    1. Badner JA, Gershon ES. Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Mol Psychiatry. 2002;7:405–411. - PubMed
    1. Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, et al. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry. 2008;13:197–207. - PMC - PubMed

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