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Use of admixture and association for detection of quantitative trait loci in the Type 2 Diabetes Genetic Exploration by Next-Generation Sequencing in Ethnic Samples (T2D-GENES) study.


Admixture mapping and association testing have been successfully applied to the detection of genes for complex diseases. Methods have also been developed to combine these approaches. As an initial step to determine the feasibility of combining admixture and association mapping in the context of whole genome sequencing, we have applied several methods to data from the Genetic Analysis Workshop 18. Here, we describe the steps necessary to carry out such a study from selection of reference populations and preprocessing of data through to the testing itself. We detected one significant result with a Bonferroni corrected p-value of 0.032 at single nucleotide polymorphism rs12639065. Computing local ancestry for Hispanic populations was challenging because there are relatively few methods by which to handle 3-way admixture, and publicly available Native American reference panels are scarce. However, combining admixture and association is a promising approach for detection of quantitative trait loci because it might be able to elevate the power of detection by combining 2 different sources of genetic signal.

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