Efficiency of typing unaffected relatives in an affected-sib-pair linkage study with single-locus and multiple tightly linked markers

Journal Article · Wed Nov 01 04:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:209916

Holmans, P; Clayton, D

In an affected-sib-pair study, the parents are often unavailable for typing, particularly for diseases of late onset. In many cases, however, it is possible to sample unaffected siblings. It is therefore desirable to assess the contribution of such siblings to the power of such a study. The likelihood ratio introduced by Risch and improved by Holmans was extended to incorporate data from unaffected siblings. Tests based on two likelihoods were considered: the full likelihood of the data, based on the identity-by-descent (IBD) sharing states of the entire sibship, and a pseudolikelihood based on the IBD sharing states of the affected pair only, using the unaffected siblings to infer parental genotypes. The latter approach was found to be more powerful, except when penetrance was high. Typing an unaffected sibling, or just one parent, was found to give only a small increase in power except when the PIC of the marker was low. Even then, typing an unaffected relative increased the overall number of individuals that had to be typed to achieve a given power. If there is no highly informative marker locus in the area under study, it may be possible to {open_quotes}build{close_quotes} one by combining the alleles from two or more neighboring tightly linked loci into haplotypes. Typing two loci gave a sizeable power increase over a single locus, but typing further loci gave much smaller gains. Building haplotypes will introduce phase uncertainties, with the result that such a system will yield less power than will a single locus with the same number of alleles. This power loss was small, however, and did not affect the conclusions regarding the worth of typing unaffected relatives. 14 refs., 2 figs., 11 tabs.

• OSTI ID: 209916
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 5 Vol. 57; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
BIOLOGICAL MARKERS
DISEASE INCIDENCE
EFFICIENCY
GENES
GENETICS
GENOTYPE
HEREDITARY DISEASES
HUMAN POPULATIONS
S CODES
STATISTICAL MODELS
STATISTICS