The haplotype-relative-risk (HRR) method for analysis of association in nuclear families

Journal Article · Tue Jun 01 04:00:00 EDT 1993 · American Journal of Human Genetics; (United States)

OSTI ID:6310382

Knapp, M; Seuchter, S A; Baur, M P ^[1]

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1. Univ. of Bonn (Germany)

One major problem in studying an association between a marker locus and a disease is the selection of an appropriate group of controls. However, this problem of population stratification can be circumvented in a quite elegant manner by family-based methods. The haplotype-relative-risk (HRR) method, which samples nuclear families with a single affected child and uses the parental haplotypes not transmitted to that child as a control individual, represents such a method for estimating the relative risk of a marker phenotype. In the special case of a recessive disease, it was already known that the equivalence of the HRR method with the classical relative risk (RR) obtained from independent samples holds only if the probability [theta] of a recombination between marker and disease locus is zero. The authors extend this result to an arbitrary mode of inheritance. Furthermore, they compare the distribution of the estimators for HRR and RR and show that, in the case of a positive linkage disequilibrium between a marker and disease allele, the distribution of the estimator for HRR is (stochastically) smaller than that for RR, irrespective of the recombination fraction. The practical implication of this result is that, for the HRR method, there is no tendency to give unduly high risk estimators, even for [theta] > 0. Finally, the authors give an expression for the standard error of the estimator for HRR by taking into account the nonindependence of transmitted and nontransmitted parental marker alleles in the case of [theta] > 0. 16 refs., 3 tabs.

• OSTI ID: 6310382
• Journal Information: American Journal of Human Genetics; (United States), Journal Name: American Journal of Human Genetics; (United States) Vol. 52:6; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

550400* -- Genetics
59 BASIC BIOLOGICAL SCIENCES
BIOLOGICAL INDICATORS
DISEASES
GENETIC MAPPING
HUMAN POPULATIONS
MAPPING
MATHEMATICS
POPULATIONS
PROBABILISTIC ESTIMATION
RISK ASSESSMENT
STATISTICS