TY - JOUR

T1 - A linkage strategy for detection of human quantitative-trait loci. I. Generalized relative risk ratios and power of sib pairs with extreme trait values

AU - Gu, Chi

AU - Rao, D. C.

N1 - Funding Information:
This work was supported, in part, by NIH and NIMH grants GM28719 and MH31302, respectively. We thank two anonymous reviewers for their many helpful comments, which improved this article.

PY - 1997/7

Y1 - 1997/7

N2 - We generalize the concept of the relative risk ratio (λ) to the case of quantitative traits, to take into account the various trait outcomes of a relative pair. Formulas are derived to express the expected proportion of genes shared identical by descent by a sib pair, in terms of the generalized λ's for sib pairs (λ(S)), parent-offspring pairs (λ(O)), and monozygotic twins (λ(M)) and in terms of the recombination fraction, with the assumption of no residual correlations. If residual correlations are nonzero among relative pairs, we assume that they are the same among sib pairs, parent- offspring pairs, and monozygotic twins, and we employ a slightly different definition for the generalized λ so that the same set of formulas still hold. The power (or, the sample size necessary) to detect quantitative-trait loci (QTLs) by use of extreme sib pairs (ESPs) is shown to be a function of the three generalized λ's. Since λ(M) can be derived by use of values of λ(S) and λ(O), estimates of the latter two λ's will suffice for the analysis of power and the necessary sample sizes of ESPs, for a QTL linkage study.

AB - We generalize the concept of the relative risk ratio (λ) to the case of quantitative traits, to take into account the various trait outcomes of a relative pair. Formulas are derived to express the expected proportion of genes shared identical by descent by a sib pair, in terms of the generalized λ's for sib pairs (λ(S)), parent-offspring pairs (λ(O)), and monozygotic twins (λ(M)) and in terms of the recombination fraction, with the assumption of no residual correlations. If residual correlations are nonzero among relative pairs, we assume that they are the same among sib pairs, parent- offspring pairs, and monozygotic twins, and we employ a slightly different definition for the generalized λ so that the same set of formulas still hold. The power (or, the sample size necessary) to detect quantitative-trait loci (QTLs) by use of extreme sib pairs (ESPs) is shown to be a function of the three generalized λ's. Since λ(M) can be derived by use of values of λ(S) and λ(O), estimates of the latter two λ's will suffice for the analysis of power and the necessary sample sizes of ESPs, for a QTL linkage study.

UR - http://www.scopus.com/inward/record.url?scp=0030843362&partnerID=8YFLogxK

U2 - 10.1086/513908

DO - 10.1086/513908

M3 - Article

C2 - 9246001

AN - SCOPUS:0030843362

VL - 61

SP - 200

EP - 210

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -