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.
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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)