Power and robustness of the linkage homogeneity test in genetic analysis of common disorders

Journal of Psychiatric ResearchPublished 1 January 1987

Françoise Clerget‐Darpoux, Marie‐Claude Babron, Catherine Bonaïti‐Pellié

DOI10.1016/0022-3956(87)90113-0

Source URL

Citations23

SJR quartileQ1

SJR score1.49

SNIP1.15

TL;DR

The power and robustness of the admixture test are studied and it is found that misspecifying genetic parameters leads to a bias in the estimates of both the recombination fraction and the proportion of linked families.

Abstract

The power and robustness of the admixture test are studied. The power of the test depends on the genetic parameters at the disease locus. In particular, the power decreases drastically with the level of penetrance. The test is robust to errors in genetic parameters provided that the recombination fraction is not fixed a priori. However, misspecifying genetic parameters leads to a bias in the estimates of both the recombination fraction and the proportion of linked families.

Keywords

Biochemistry, Genetics and Molecular Biology

BiometricsEffects of Misspecifying Genetic Parameters in Lod Score Analysis

446 Citations1986Françoise Clerget‐Darpoux, Catherine Bonaïti‐Pellié +1 more

The lod score method is widely used to test linkage and to estimate the recombination fraction between a disease locus and a marker locus, but the power of the linkage test is sensitive to the degree of dominance, and slightly to the penetrance, but not to the gene frequency.

PubMedThe detection and estimation of linkage between the genes for elliptocytosis and the Rh blood type.

437 Citations1956Newton E. Morton

The data on this subject are unusually extensive, and they provide strong evidence of an autosomal linkage in man.

View PDF

Annals of Human GeneticsTesting for heterogeneity of recombination fraction values in Human Genetics

299 Citations1963Cedric A. B. Smith

A method is described for the detection of heterogeneity of recombination fraction values in human data using a comparison of likelihood values, applied to the data on elliptocytosis and rhesus previously considered by Morton (1956), together with some new data reported by Bannerman & Renwick (1962).

Annals of Human GeneticsLinkage analysis and family classification under heterogeneity

180 Citations1983Jürg Ott

Morton's homogeneity test is compared with another test (Admixture test) with respect to significance level, power, parameter estimation and classification of families for the mixture situation.

PubMedThe search for heterogeneity in insulin-dependent diabetes mellitus (IDDM): linkage studies, two-locus models, and genetic heterogeneity.

123 Citations1983Susan E. Hodge, Carol E. Anderson +3 more

There was little evidence for heterogeneity within any of the lod scores, under either the Predivided-Sample Test or the Admixture Test, and results continued to support linkage of IDDM with three chromosome 6 markers: HLA, BF, and GLO.

Annals of Human GeneticsX‐linkage and genetic heterogeneity in bipolar‐related major affective illness: reanalysis of linkage data

109 Citations1982Neil Risch, Miron Baron

Recently published pedigree series are reanalysed for linkage using a systematic method of pedigree analysis (Liped 3) with an accurate age‐of‐onset correction and results are consistent with known linkages on the X chromosome.

PubMedDetecting linkage for genetically heterogeneous diseases and detecting heterogeneity with linkage data.

81 Citations1986Luigi Luca Cavalli-Sforza, Mary‐Claire King

This work has answered the questions for the most important types of matings under specified conditions: linkage phase known or unknown, number of alleles involved in the cross at the marker locus, and different numbers of affected and unaffected children.