Title: Reconstructing the Genetic Demography of the United States. R. Sebro1, N. Laird2, N. Risch3,4,5 1) Radiology; Genetics, University of California, San Francisco, San Francisco, CA; 2) Department of Biostatistics, Harvard School for Public Health; 3) Institute for Human Genetics, University of California, San Francisco;; 4) Department of Epidemiology and Biostatistics, University of California, San Francisco; 5) Division of Research, Kaiser Permanente, Oakland, CA.

   The United States (U.S) is a complex, multiethnic society shaped by immigration and admixture, but the extent to which these forces influence the overall population genetic structure of the U.S is unknown. We utilized self-reported ancestry data collected from the decennial U.S Census 2010 and allele frequency data from over 2000 SNPs for over 40 of the most common ancestries in the U.S. that were available from the Pan Asian Single Nucleotide Polymorphism (PASNP), Population Reference Sample (POPRES), 1000 Genomes, and Human Genome Diversity Panel (HGDP) databases. We utilized the relative proportions of individuals of each ancestry within each county, state, region and nation and calculate the weighted average allele frequency in these areas. We reconstructed the genetic demography of the U.S by examining the geographic distribution of Wrights Fst. Shannons diversity index, H was calculated to assess the apportionment of genetic diversity at the county, state, regional and national level. This analysis was repeated stratifying by race/ethnicity. We analyzed households with spouses, using the phi-coefficient as a measure of assortative mating for ancestry. This analysis was repeated stratifying by age of the spouses (older or younger than 50). Most of the genetic diversity is between ancestries within county, but this varies by race/ethnicity, and ranges from 95% for Whites to 43% for Hispanics illustrating that the White ancestries are relatively homogeneously scattered throughout the U.S whereas the Hispanic ancestries show significant clustering by geography. Analysis of the mating patterns show strong within ethnicity assortative mating for American Indian/Alaska Natives, Asians, Blacks, Hispanic, Native Hawaiians/Pacific Islanders, and Whites, with = 0.30, 0.864, 0.92, 0.863, 0.478 and 0.832 respectively (P<1x10-324 for each) and significantly less correlation in the younger cohort. These results show demographic patterns of social homogamy which are slowly decreasing over time. One major implication is that data collected from different locations around the U.S are susceptible to both within- and between-location population genetic substructure, leading to potential biases in population-based association studies.

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