Antibodies in the Families of Thyrotoxic Patients

Evans, A. W.; Woodrow, J. C.; McDougall, Catherine; Chew, Andrew; Evans, R.Winston

doi:10.1016/s0140-6736(67)92539-1

Cited by 46 publications

(8 citation statements)

References 11 publications

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“…type 2 diabetes, 3·5), hence linkage analysis has been more successful in single gene disorders. In Graves' disease, we have estimated a s of around 10 on the basis of epidemiological data provided in studies by Bartels (1941) and Howell-Evans et al (1967). However, follow-up data from the Whickam survey have shown that Graves' disease is more common than previously believed, with a prevalence of approximately 2% (Vanderpump et al 1995).…”

Section: Classical Linkage Analysismentioning

confidence: 99%

The different approaches to the genetic analysis of autoimmune thyroid disease

Allahabadia¹,

Gough²

1999

Journal of Endocrinology

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Graves' disease and Hashimoto's thyroiditis are organspecific autoimmune disorders of multifactorial aetiology with a polygenic mode of inheritance. Familial clustering and twin studies provide evidence for a genetic predisposition. Three main approaches have been used in the search for susceptibility loci: population-based case-control studies, classical linkage analysis, and intrafamilial linkage disequilibrium. Case-control studies are a sensitive method of gene detection and the collection of subjects is resource-efficient. However, they require prior knowledge of a candidate gene and are prone to inconsistent results due to false positives that may arise from population mismatch. Linkage analysis is a powerful tool for detecting 'major' genes that does not require a candidate gene and is, therefore, a means of genome screening. This method, however, has limited power to detect genes of 'modest' effect, and the collection of sibpairs and multiple family members may be difficult. Intrafamilial linkage disequilibrium analysis is more sensitive than classical linkage analysis, requires only one affected offspring, and eliminates population mismatch. This approach has confirmed linkage disequilibrium of the HLA region with Graves' disease, previously not detected by linkage analysis. Knowledge of a candidate locus is required, however, and this method cannot, therefore, at present be used for genome screening. It is likely that a combination of all three approaches will be required to identify susceptibility loci for autoimmune thyroid disease.

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Section: Classical Linkage Analysismentioning

confidence: 99%

The different approaches to the genetic analysis of autoimmune thyroid disease

Allahabadia¹,

Gough²

1999

Journal of Endocrinology

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“…However, these results have to be interpreted with caution because there is always a risk of bias when hospitalized subjects are used as probands in family studies (20), ie, the probability for a family to become ascertained is a function of the number of affected subjects in that family. Bartels (9) and Martin and Fisher (10) found that the probands' sisters were affected more often than the parents (mothers), whereas in the study of Howel-Evans et al (11), the mothers were more frequently affected. Stenszky et al (12), however, found an almost equal distribution of GD among the probands' female relatives.…”

Section: Family and Twin Studiesmentioning

confidence: 97%

“…In Caucasians, a role for heredity in GD is suggested by the aggregation of hyperthyroidism within families (9)(10)(11)(12)(13) and by higher concordance rates for MZ twins than DZ twins (6)(7)(8). Family and twin studies are the classic meth- 1 Department of Endocrinology M, Odense University Hospital, Odense C, Denmark.…”

Section: Family and Twin Studiesmentioning

confidence: 99%

“…portance of genetic factors in disease susceptibility is at present largely unknown (3). Family studies A family history of hyperthyroidism can be obtained in up to 50% of subjects with GD/hyperthyroidism1 (9,10), and family studies have demonstrated a familiar clustering of GD/hyperthyroidism (9)(10)(11)(12)(13)19). Family studies, where ascertainment has been based on sampling of hospital patients, indicate that GD/hyperthyroidism occurs in about 1% and 5% of the probands' first-degree male and female relatives, respectively (Table 1).…”

Section: Family and Twin Studiesmentioning

confidence: 99%

“…Martin and Fisher (10) found evidence for the inheritance of a single recessive predisposing factor favorable to GD and perhaps necessary for its occurrence. In subsequent studies (11,12,19), the familial occurrence of GD did not seem to follow any simple Mendelian pattern of inheritance, and a multifactorial mode of inheritance has therefore been suggested (21,22). Moreover, the fact that no single gene has been shown to be either necessary for the development of GD or sufficient to cause it, implies that GD is under the influence of multiple genes and probably of variable penetrance (4).…”

Section: Family and Twin Studiesmentioning

confidence: 99%

See 2 more Smart Citations

What is the Evidence of Genetic Factors in the Etiology of Graves' Disease? A Brief Review

Brix¹,

Kyvik²,

Hegedűs³

1998

Thyroid

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Graves' disease (GD) is generally thought of as a multifactorial disorder in which genetic susceptibility interacts with environmental and endogenous factors to cause disease. The importance of genetic factors is suggested by the clustering of GD within families and by a higher concordance rate for disease in monozygotic than in dizygotic twins. This has, however, recently been shown to be less pronounced than previously thought. During the last decade much effort has been put into characterization of the genetic background of GD. Until recently, most studies have examined associations between GD and the human leukocyte antigen (HLA) region, but recent advances in molecular techniques have opened the way for whole genome screening. A number of HLA and non-HLA candidate genes have been proposed, but despite several large investigations within multiplex families no major susceptibility genes have been identified. This brief review discusses relevant articles published from 1940 through 1997 regarding the influence of genetic factors in the etiology of GD. Ongoing studies focus on whole genome screening in multiplex families as well as population-based twin studies. However, the possibility of GD being a heterogeneous disease without a single well-defined genotype and phenotype should be left open.

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Complex segregation analysis of antibodies to thyroid peroxidase in old order amish families

Zakarija

et al. 1993

Am. J. Med. Genet.

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Autoimmune thyroid disease (AITD) may be characterized by the measurement in serum of antibodies to thyroid peroxidase. A population of Old Order Amish individuals and families was investigated to determine the prevalence of these antibodies and to examine hypotheses about the mode of transmission of thyroid antibodies. Complex segregation analyses were performed on 4 large multigenerational Old Order Amish families composed of 26 nuclear families containing 199 first degree relatives. Several alternative hypotheses of genetic transmission were examined. Hypotheses of no transmission, polygenic inheritance, single locus transmission, and mixed inheritance were compared. The analyses incorporated population prevalences obtained from a random sample of individuals. Results suggest that the pattern of transmission of thyroid antibodies in these families is consistent with a mixed model in which the major gene is transmitted in an autosomal dominant pattern. The mixed model postulates that there is a single gene of major effect as well as a polygenic component that can act separately and/or together to confer susceptibility for this phenotype. The parameter estimates for the major locus are: gene frequency (q), 0.16 +/- 0.01; maximum male penetrance, 0.35; and maximum female penetrance, 0.70. The heritability of the polygenic background is estimated at 0.41.

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Antibodies in the Families of Thyrotoxic Patients

Cited by 46 publications

References 11 publications

The different approaches to the genetic analysis of autoimmune thyroid disease

The different approaches to the genetic analysis of autoimmune thyroid disease

What is the Evidence of Genetic Factors in the Etiology of Graves' Disease? A Brief Review

Complex segregation analysis of antibodies to thyroid peroxidase in old order amish families

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