Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Ancestral processes for non-neutral models of complex diseases.
AU - Fearnhead, Paul
PY - 2003/3
Y1 - 2003/3
N2 - We consider non-neutral models for unlinked loci, where the fitness of a chromosome or individual is not multiplicative across loci. Such models are suitable for many complex diseases, where there are gene-interactions. We derive a genealogical process for such models, called the complex selection graph (CSG). This coalescent-type process is related to the ancestral selection graph, and is derived from the ancestral influence graph by considering the limit as the recombination rate between loci gets large. We analyse the CSG both theoretically and via simulation. The main results are that the gene-interactions do not produce linkage disequilibrium, but do produce dependencies in allele frequencies between loci. For small selection rates, the distributions of the genealogy and the allele frequencies at a single locus are well-approximated by their distributions under a single locus model, where the fitness of each allele is the average of the true fitnesses of that allele with respect to the distribution of alleles at other loci.
AB - We consider non-neutral models for unlinked loci, where the fitness of a chromosome or individual is not multiplicative across loci. Such models are suitable for many complex diseases, where there are gene-interactions. We derive a genealogical process for such models, called the complex selection graph (CSG). This coalescent-type process is related to the ancestral selection graph, and is derived from the ancestral influence graph by considering the limit as the recombination rate between loci gets large. We analyse the CSG both theoretically and via simulation. The main results are that the gene-interactions do not produce linkage disequilibrium, but do produce dependencies in allele frequencies between loci. For small selection rates, the distributions of the genealogy and the allele frequencies at a single locus are well-approximated by their distributions under a single locus model, where the fitness of each allele is the average of the true fitnesses of that allele with respect to the distribution of alleles at other loci.
KW - Ancestral influence graph
KW - Ancestral selection graph
KW - Complex diseases
KW - Gene-interaction
KW - Genic selection
KW - Linkage disequilibrium
U2 - 10.1016/S0040-5809(02)00049-7
DO - 10.1016/S0040-5809(02)00049-7
M3 - Journal article
VL - 63
SP - 115
EP - 130
JO - Theoretical Population Biology
JF - Theoretical Population Biology
SN - 1096-0325
IS - 2
ER -