TY - JOUR

T1 - Gamete-competition models

AU - Sinsheimer, Janet S.

AU - Blangero, John

AU - Lange, Kenneth

N1 - Funding Information:
The authors thank R. Cantor for her helpful suggestions; G. M. Lathrop, B. Keavney, and C. McKenzie for the ACE data; M. Stern and P. O’Connell for the diabetes data; and B. C. Hennis for the HRG data. The research was supported in part by USPHS grants CA16042 (to J.S.S.), DK47482 (to J.B.), DK42273 (to J.B.), MH59490 (to J.B.), and GM53275 (to K.L.).

PY - 2000

Y1 - 2000

N2 - The gamete-competition model is an application of the Bradley-Terry model for ranking of sports teams. If allele i of a marker locus is assigned parameter τ(i) > 0, then the probability that a parent with heterozygous genotype i/j transmits allele i is Pr (i/j→i) = τ(i)/(τ(i) + τ(i)). Mendelian segregation corresponds to the choice τ(i) = 1 for all i. To test whether Mendelian segregation is true, one can estimate the τ(i) from pedigree data and perform a likelihood-ratio test under the constraint that one τ(i) equals 1. Although this procedure generates an interesting method for performance of segregation analysis with a marker locus, its real promise lies in generalization of the transmission/disequilibrium test. Quantitative as well as qualitative outcomes can be considered. The gamete-competition model uses full pedigree data and gives an estimate of the strength of transmission distortion to affected children for each allele. Covariates are incorporated by rewriting of τ(i) = exp (β(t)x(k)), where β is a parameter vector and x(k) is a covariate vector for the kth transmitted gamete. Examples of covariates include disease-severity indicators for the child, sex of the child, or repeat number for tandem-repeat alleles.

AB - The gamete-competition model is an application of the Bradley-Terry model for ranking of sports teams. If allele i of a marker locus is assigned parameter τ(i) > 0, then the probability that a parent with heterozygous genotype i/j transmits allele i is Pr (i/j→i) = τ(i)/(τ(i) + τ(i)). Mendelian segregation corresponds to the choice τ(i) = 1 for all i. To test whether Mendelian segregation is true, one can estimate the τ(i) from pedigree data and perform a likelihood-ratio test under the constraint that one τ(i) equals 1. Although this procedure generates an interesting method for performance of segregation analysis with a marker locus, its real promise lies in generalization of the transmission/disequilibrium test. Quantitative as well as qualitative outcomes can be considered. The gamete-competition model uses full pedigree data and gives an estimate of the strength of transmission distortion to affected children for each allele. Covariates are incorporated by rewriting of τ(i) = exp (β(t)x(k)), where β is a parameter vector and x(k) is a covariate vector for the kth transmitted gamete. Examples of covariates include disease-severity indicators for the child, sex of the child, or repeat number for tandem-repeat alleles.

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U2 - 10.1086/302826

DO - 10.1086/302826

M3 - Article

C2 - 10712230

AN - SCOPUS:0033941557

VL - 66

SP - 1168

EP - 1172

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 3

ER -