Population Genetic Structure in the South Pacific: Prospects for Identifying Disease Susceptibility Genes in New Zealanders with Polynesian Ancestry
Rodney Lea1, Geoffrey Chambers2
1Rod.Lea@vuw.ac.nz, Institute of Molecular Systematics; 2Geoff.Chambers@vuw.ac.nz, Institute of Molecular Systematics
In humans, the genetic variation that is due to differences between population groups (~10%) influences traits such as physical appearance, disease susceptibility and response to medication. In New Zealand, cardiovascular diseases, particularly stroke and coronary heart disease, and associated risk factors (ie. hypertension and obesity) are significantly over-represented in Polynesian groups compared with Europeans. It has been hypothesised that the increased occurrence of these disorders in Polynesian groups arises due to higher frequencies of susceptibility genes and/or genetic interaction because of intermarriage with Europeans (admixture). Identification of the ethnic-specific genetic determinants of disease is of substantial public health significance in countries like New Zealand because mode of disease treatment may ultimately depend on it.
Case-control studies incorporating genetic admixture and/or correcting for population substructure are a powerful design for identifying loci that contribute to complex traits like cardiovascular disease. The genetic markers that distinguish ancestry (ie. have large allele frequency differences among groups) are important for understanding patterns of genetic structure within a population comprised of multiple ethnic and/or admixed groups such as is found in New Zealand. Our study will utilise existing multi-locus genotype data from unlinked microsatellite markers to describe the genetic structure in different Polynesian (Maori, Samoan, Tongan), European and admixed populations.
Specifically, our strategy is to employ advanced bioinformatics techniques involving 1. A weighted least squares method to quantify admixture (ancestral) proportions in different Polynesian populations, 2. A model-based clustering method for use on multilocus genotype data to infer population structure and assign individuals to populations, even in the presence of admixture. For New Zealand, this analysis may have important implications for identifying disease genes by admixture linkage disequilibrium mapping and determining ethnicity by DNA marker instead of patient self-report, respectively. It is hoped that our results will provide valuable directions for disease gene identification and Polynesian-specific treatments in predisposed New Zealanders with Polynesian Ancestry.