Combined Segregation and Linkage Analysis of Graves Disease with a Thyroid Autoantibody Diathesis

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1994 Sep 1

PMID 8079993

Citations 10

Authors

D C Shields

S Ratanachaiyavong

A M McGregor

A Collins

N E Morton

Affiliations

Soon will be listed here.

Abstract

Combined segregation and linkage analysis is a powerful technique for modeling linkage to diseases whose etiology is more complex than the effect of a well-described single genetic locus and for investigating the influence of single genes on various aspects of the disease phenotype. Graves disease is familial and is associated with human leukocyte antigen (HLA) allele DR3. Probands with Graves disease, as well as close relatives, have raised levels of thyroid autoantibodies. This phenotypic information additional to affection status may be considered by the computer program COMDS for combined segregation and linkage analysis, when normals are classified into diathesis classes of increasing thyroid autoantibody titer. The ordinal model considers the cumulative odds of lying in successive classes, and a single additional parameter is introduced for each gene modeled. Distributional assumptions are avoided by providing estimates of the population frequencies of each class. Evidence for linkage was increased by considering the thyroid autoantibody diathesis and by testing two-locus models. The analysis revealed evidence for linkage to HLA-DR when the strong coupling of the linked locus to allele DR3 was considered (lod score of 6.6). Linkage analysis of the residual variation revealed no evidence of linkage to Gm, but a suggestion of linkage to Km.

Citing Articles

Role of genetic and non-genetic factors in the etiology of Graves' disease.

Marino M, Latrofa F, Menconi F, Chiovato L, Vitti P J Endocrinol Invest. 2014; 38(3):283-94.

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Immunogenetic mechanisms leading to thyroid autoimmunity: recent advances in identifying susceptibility genes and regions.

Brand O, Gough S Curr Genomics. 2012; 12(8):526-41.

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Evaluation of hearing loss in patients with Graves' disease.

Berker D, Karabulut H, Isik S, Tutuncu Y, Ozuguz U, Erden G Endocrine. 2011; 41(1):116-21.

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Integrating genotypic data with transcriptomic and proteomic data.

Shields D, OHalloran A Comp Funct Genomics. 2008; 3(1):22-7.

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Lack of association of VDR gene polymorphisms with thyroid autoimmune disorders: familial and case/control studies.

Maalej A, Petit-Teixeira E, Chabchoub G, Ben Hamad M, Rebai A, Farid N J Clin Immunol. 2007; 28(1):21-5.

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