TY - JOUR

T1 - Linkage analysis of complex traits using affected sibpairs

T2 - Effects of single-locus approximations on estimates of the required sample size

AU - Todorov, A. A.

AU - Borecki, I. B.

AU - Rao, D. C.

PY - 1997

Y1 - 1997

N2 - We investigated the power of the affected sibpair method for detecting a disease locus when the disease is inherited through two bi-allelic loci. The power was computed for all possible values of the gene frequencies and penetrances that lead to a given population prevalence and a given sibling relative risk. A method to generate rapidly all possible models that give a specific population prevalence and relative risk is provided. We applied it to the case of a two-locus disease with a prevalence of 10% and a low sibling relative risk of 1.5. For this particular example, regardless of the true underlying model, a sample size (N ≃ 450 for α = 0.05, N ≃ 1,500 for α = 0.0001) may be determined such that one would expect enough power (0.80) to detect at least one of the two disease genes. In addition to the general case, we examined a special class of models in which the marginal penetrances at each locus are either recessive or dominant. In this instance, the gene frequencies were excellent predictors of the power afforded by a particular sample size. These methods have been implemented in a C program called SIBPOWER which is freely available from the first author. With this program, investigators can perform their own power calculations for any two-locus model of their choice thus avoiding the need to use single-locus approximations that may grossly underestimate the necessary sample size.

AB - We investigated the power of the affected sibpair method for detecting a disease locus when the disease is inherited through two bi-allelic loci. The power was computed for all possible values of the gene frequencies and penetrances that lead to a given population prevalence and a given sibling relative risk. A method to generate rapidly all possible models that give a specific population prevalence and relative risk is provided. We applied it to the case of a two-locus disease with a prevalence of 10% and a low sibling relative risk of 1.5. For this particular example, regardless of the true underlying model, a sample size (N ≃ 450 for α = 0.05, N ≃ 1,500 for α = 0.0001) may be determined such that one would expect enough power (0.80) to detect at least one of the two disease genes. In addition to the general case, we examined a special class of models in which the marginal penetrances at each locus are either recessive or dominant. In this instance, the gene frequencies were excellent predictors of the power afforded by a particular sample size. These methods have been implemented in a C program called SIBPOWER which is freely available from the first author. With this program, investigators can perform their own power calculations for any two-locus model of their choice thus avoiding the need to use single-locus approximations that may grossly underestimate the necessary sample size.

KW - Affected sibpair method

KW - Complex traits

KW - Epistasis

KW - Power analysis

KW - Two- locus genetic models

UR - http://www.scopus.com/inward/record.url?scp=0030829369&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1098-2272(1997)14:4<389::AID-GEPI4>3.0.CO;2-Z

DO - 10.1002/(SICI)1098-2272(1997)14:4<389::AID-GEPI4>3.0.CO;2-Z

M3 - Article

C2 - 9271711

AN - SCOPUS:0030829369

SN - 0741-0395

VL - 14

SP - 389

EP - 401

JO - Genetic Epidemiology

JF - Genetic Epidemiology

IS - 4

ER -