Sex chromosomes and genetic association studies 英文参考文献.docVIP

Review Sex chromosomes and genetic association studies David G Clayton Address: Wellcome Trust/Juvenile Diabetes Research Foundation Diabetes and Inflammation Laboratory, Cambridge University, Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome Trust/MRC Building, Addenbrooke’s Hospital, Cambridge CB2 0XY, UK. Email: david.clayton@cimr.cam.ac.uk Case-control studies Before turning to the special problems presented by the X chromosome, we shall review simple methods of analysis for autosomal loci in case-control studies. Abstract Although the literature concerning statistical testing for genotype- phenotype association in family-based and population-based studies is very extensive, until recently the sex chromosomes have received little attention. Here it is shown that the X chromosome in particular presents special problems with Autosomal loci Counting chromosomes respect to efficient analysis of mixed-sex population studies, and as a result of X inactivation. This paper reviews recent developments in approaching these problems. Many early analyses of association between a binary phenotype and a genetic marker used simple tests for association in contingency tables in which cell entries were counts of chromosomes rather than people. Thus, for an autosomal locus, the total cell count is twice the number of subjects studied, and associations were tested simply by comparing allele frequencies between cases and controls. In the diallelic case, this reduces to the analysis of a 2 × 2 table (Table 1). The most commonly used test was the familiar chi-squared test for association which, here, has one degree of freedom (df). The calculations of the chi- squared test statistic, T say, can be broken down in a manner which aids later discussion as follows, where N is the