The 82nd Annual Meeting of the American Association of Physical Anthropologists (2013)


A variance component method for analyzing the effect of ancestry in admixed family-based genetic studies

ELLEN E. QUILLEN1, LAURA ALMASY1, RAVINDRANATH DUGGIRALA1, JOANNE E. CURRAN1, MELANIE C. CARLESS1, THOMAS D. DYER1, JEAN W. MACCLEUR1, DONNA M. LEHMAN3, ANTHONY COMUZZIE1, HARALD HH. GÖRING1, DAVID C. GLAHN2 and JOHN BLANGERO1.

1Department of Genetics, Texas Biomedical Research Institute, 2Department of Psychiatry, School of Medicine, Yale University, 3Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio

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The appearance of similar regions of extended linkage disequilibrium (LD) found in pedigrees and created by admixture has been described previously and forms the basis of admixture mapping which can increase power to detect genes influencing normal or pathological traits that vary between parental populations. However, admixture LD has not previously been incorporated into methods which use the admixture present in many U.S. populations to increase power in family-based designs. This is achieved by the incorporation of shared ancestry information across multiple pedigrees by use of additional matrices of relatedness as calculated directly from biogeographic ancestry information found in dense genotype data. As currently implemented, this is an extension of the variance component methods utilized in SOLAR, but the theoretical basis could be applied to other methods. Depending on computing power, the ancestry-relatedness matrix can be calculated either as a genome-wide estimate or on a locus-specific basis, which will increase power for some traits. The utility of this method is illustrated by examination of Mexican American families enrolled in the San Antonio Family Study analyzed using both conventional linkage and association methods and with the inclusion of an additional ancestry matrix. As compared to studies of unrelated individuals, siblings, or nuclear families, the analysis of extended pedigrees greatly improves power by increasing the total number of contrasts that can be considered. The inclusion of an overarching relationship matrix based on shared ancestry provides a method for linking extended pedigrees into a single meta-pedigree for a yet more powerful analysis.

This work is funded by NIH grants R01 MH059490, P01 HL061622, and R01 GM031575

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