Population substructure in Cache County, Utah: the Cache County study

BMC Bioinformatics, May 2014

Background Population stratification is a key concern for genetic association analyses. In addition, extreme homogeneity of ethnic origins of a population can make it difficult to interpret how genetic associations in that population may translate into other populations. Here we have evaluated the genetic substructure of samples from the Cache County study relative to the HapMap Reference populations and data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results Our findings show that the Cache County study is similar in ethnic diversity to the self-reported "Whites" in the ADNI sample and less homogenous than the HapMap CEU population. Conclusions We conclude that the Cache County study is genetically representative of the general European American population in the USA and is an appropriate population for conducting broadly applicable genetic studies.

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Population substructure in Cache County, Utah: the Cache County study

Aaron R Sharp 0 3 Perry G Ridge 0 3 Matthew H Bailey 0 3 Kevin L Boehme 0 3 Maria C Norton 1 2 3 4 JoAnn T Tschanz 2 3 4 Ronald G Munger 3 4 6 Christopher D Corcoran 3 4 5 John SK Kauwe 0 3 Alzheimer's Disease Neuroimaging Initiative (ADNI) 3 0 Department of Biology, Brigham Young University , Provo, Utah , USA 1 Department of Family Consumer and Human Development , Utah State 2 Department of Psychology, Utah State University , Logan, Utah , USA 3 University , Logan, Utah , USA 4 Center for Epidemiologic Studies, Utah State University , Logan, Utah , USA 5 Department of Mathematics and Statistics, Utah State University , Logan, Utah , USA 6 Department of Nutrition, Dietetics, and Food Sciences, Utah State University , Logan, Utah , USA Background: Population stratification is a key concern for genetic association analyses. In addition, extreme homogeneity of ethnic origins of a population can make it difficult to interpret how genetic associations in that population may translate into other populations. Here we have evaluated the genetic substructure of samples from the Cache County study relative to the HapMap Reference populations and data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Results: Our findings show that the Cache County study is similar in ethnic diversity to the self-reported Whites in the ADNI sample and less homogenous than the HapMap CEU population. Conclusions: We conclude that the Cache County study is genetically representative of the general European American population in the USA and is an appropriate population for conducting broadly applicable genetic studies. - Background Cryptic population differences due to heterogeneity have confounding effects on association studies, especially when analyzing complex traits and gene-gene interactions. It is also possible that genetic associations that are observed in very homogeneous populations may not be generalizable to other populations. The Cache County study is a large longitudinal cohort study of memory, health, and aging that was initiated in 1994. This sample of 5,092 individuals represents approximately 90% of the Cache County population aged 65 and older at that time. These data are a valuable resource in genetic studies of Alzheimers disease (AD), as well as otherdiscussion forms of dementia [1]. The founding populations and migrations to Utah by early members of the Church of Jesus Christ of Latter Day Saints have been studied extensively[2-4]. These studies have concluded that due to the large founding population, high rates of gene flow and diversity of source populations the Utah population has allele frequencies that are quite similar to the general European American population in the United States. As it was collected from one county in Utah, there have been questions as to how the genetic diversity in the Cache County sample compares to that of more broadly collected European American samples and whether that diversity affects the validity or generalizability of results obtained from the Cache County study. The Cache County study is a large longitudinal cohort study of memory, health, and aging that was initiated in 1994. This sample of 5,092 individuals represents approximately 90% of the Cache County population aged 65 and older at that time. These data are a valuable resource in genetic studies of Alzheimers disease (AD), as well as other forms of dementia [1]. The founding populations and migrations to Utah by early members of the Church of Jesus Christ of Latter Day Saints have been studied extensively[2-4]. These studies have concluded that due to the large founding population, high rates of gene flow and diversity of source populations the Utah population has allele frequencies that are quite similar to the general European American population in the United States. As it was collected from one county in Utah, there have been questions as to how the genetic diversity in the Cache County sample compares to that of more broadly collected European American samples and whether that diversity affects the validity or generalizability of results obtained from the Cache County study. The purpose of this study is to compare the genetic structure of the Cache County study, which was collected from one county in northern Utah, to that of the Alzheimers Disease Neuroimaging Initiative, a sample that was collected from several sites around the USA, and data from several other populations from the International HapMap Project. Methods Sample collection and genotyping The Cache County study originally included 5,092 permanent residents of Cache County over the age of 64. Details of collection methods and demographics of the Cache County samples have been reported previously [1]. Briefly, samples underwent four triennial waves of data collection in a multi-stage dementia screening and assessment protocol. DNA was obtained from blood and buccal swabs as described by Breitner et al. [1] All study procedures were a (...truncated)


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Aaron R Sharp, Perry G Ridge, Matthew H Bailey, Kevin L Boehme, Maria C Norton, JoAnn T Tschanz, Ronald G Munger, Christopher D Corcoran, John SK Kauwe, . Population substructure in Cache County, Utah: the Cache County study, BMC Bioinformatics, 2014, pp. S8, 15, DOI: 10.1186/1471-2105-15-S7-S8