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A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes.

Abstract：

:A stepwise logistic-regression procedure is proposed for evaluation of the relative importance of variants at different sites within a small genetic region. By fitting statistical models with main effects, rather than modeling the full haplotype effects, we generate tests, with few degrees of freedom, that are likely to be powerful for detecting primary etiological determinants. The approach is applicable to either case/control or nuclear-family data, with case/control data modeled via unconditional and family data via conditional logistic regression. Four different conditioning strategies are proposed for evaluation of effects at multiple, closely linked loci when family data are used. The first strategy results in a likelihood that is equivalent to analysis of a matched case/control study with each affected offspring matched to three pseudocontrols, whereas the second strategy is equivalent to matching each affected offspring with between one and three pseudocontrols. Both of these strategies require you be able to infer parental phase (i.e., those haplotypes present in the parents). Families in which phase cannot be determined must be discarded, which can considerably reduce the effective size of a data set, particularly when large numbers of loci that are not very polymorphic are being considered. Therefore, a third strategy is proposed in which knowledge of parental phase is not required, which allows those families with ambiguous phase to be included in the analysis. The fourth and final strategy is to use conditioning method 2 when parental phase can be inferred and to use conditioning method 3 otherwise. The methods are illustrated using nuclear-family data to evaluate the contribution of loci in the HLA region to the development of type 1 diabetes.

journal_name

Am J Hum Genet

journal_title

American journal of human genetics

authors

Cordell HJ,Clayton DG

doi

10.1086/338007

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

124-41

issue

eissn

0002-9297

issn

1537-6605

pii

S0002-9297(07)61288-9

journal_volume

pub_type

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A unified stepwise regression procedure for evaluating the relative effects of polymorphisms within a gene using case/control or family data: application to HLA in type 1 diabetes.