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Population Allele Frequency (population + allele_frequency)
Selected AbstractsWorldwide allele frequencies of the human apolipoprotein E gene: Climate, local adaptations, and evolutionary historyAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2010Dan T.A. Eisenberg Abstract The ,4 allele of the apolipoprotein E (APOE) gene is associated with increased cholesterol levels and heart disease. Population allele frequencies of APOE have previously been shown to vary, with ,4 frequencies generally increasing with latitude. We hypothesize that this trend resulted from natural selection protecting against low-cholesterol levels. In high-latitude cold environments and low-latitude hot environments, metabolic rate is elevated, which could require higher cholesterol levels. To explore this hypothesis, we compiled APOE allele frequencies, latitude, temperature, and elevation from populations around the world. ,4 allele frequencies show a curvilinear relationship with absolute latitude, with lowest frequencies found in the mid-latitudes where temperatures generally require less expenditure on cooling/thermogenesis. Controlling for population structure in a subset of populations did not appreciably change this pattern of association, consistent with selection pressures that vary by latitude shaping ,4 allele frequencies. Temperature records also predict APOE frequency in a curvilinear fashion, with lowest ,4 frequencies at moderate temperatures. The model fit between historical temperatures and ,4 is less than between latitude and ,4, but strengthened after correcting for estimated temperature differences during the Paleolithic. Contrary to our hypothesis, we find that elevation did not improve predictive power, and an integrated measure of the cholesterol effect of multiple APOE alleles was less related to latitude than was ,4 alone. Our results lend mixed support for a link between past temperature and human APOE allele distribution and point to the need to develop better models of past climate in future analyses. Am J Phys Anthropol 143:13,20, 2010. © 2010 Wiley-Liss, Inc. [source] Replication of the tumor necrosis factor receptor,associated factor 1/complement component 5 region as a susceptibility locus for rheumatoid arthritis in a European family-based studyARTHRITIS & RHEUMATISM, Issue 9 2008F. A. S. Kurreeman Objective We recently showed, using a candidate gene approach in a case,control association study, that a 65-kb block encompassing tumor necrosis factor receptor,associated factor 1 (TRAF1) and C5 is strongly associated with rheumatoid arthritis (RA). Compared with case,control association studies, family-based studies have the added advantage of controlling potential differences in population structure and are not likely to be hampered by variation in population allele frequencies, as is seen for many genetic polymorphisms, including the TRAF1/C5 locus. The aim of this study was to confirm this association in populations of European origin by using a family-based approach. Methods A total of 1,356 western European white individuals from 452 "trio" families were genotyped for the rs10818488 polymorphism, using the TaqMan allelic discrimination assay. Results We observed evidence for association, demonstrating departure from Mendel's law, with an overtransmission of the rs10818488 A allele (A = 55%; P = 0.036). By taking into consideration parental phenotypes, we also observed an increased A allele frequency in affected versus unaffected parents (A = 64%; combined P = 0.015). Individuals carrying the A allele had a 1.2-fold increased risk of developing RA (allelic odds ratio 1.24, 95% confidence interval 1.04,1.50). Conclusion Using a family-based study that is robust against population stratification, we provide evidence for the association of the TRAF1/C5 rs10818488 A allele and RA in populations of European descent, further substantiating our previous findings. Future functional studies should yield insight into the biologic relevance of this locus to the pathways involved in RA. [source] A prevalence-based association test for case-control studiesGENETIC EPIDEMIOLOGY, Issue 7 2008Kelli K. Ryckman Abstract Genetic association is often determined in case-control studies by the differential distribution of alleles or genotypes. Recent work has demonstrated that association can also be assessed by deviations from the expected distributions of alleles or genotypes. Specifically, multiple methods motivated by the principles of Hardy-Weinberg equilibrium (HWE) have been developed. However, these methods do not take into account many of the assumptions of HWE. Therefore, we have developed a prevalence-based association test (PRAT) as an alternative method for detecting association in case-control studies. This method, also motivated by the principles of HWE, uses an estimated population allele frequency to generate expected genotype frequencies instead of using the case and control frequencies separately. Our method often has greater power, under a wide variety of genetic models, to detect association than genotypic, allelic or Cochran-Armitage trend association tests. Therefore, we propose PRAT as a powerful alternative method of testing for association. Genet. Epidemiol. 2008. © 2008 Wiley-Liss, Inc. [source] Optimal Two-Stage Design for Case-Control Association Analysis Incorporating Genotyping ErrorsANNALS OF HUMAN GENETICS, Issue 3 2008Y. Zuo Summary Two-stage design is a cost effective approach for identifying disease genes in genetic studies and it has received much attention recently. In general, there are two types of two-stage designs that differ on the methods and samples used to measure allele frequencies in the first stage: (1) Individual genotyping is used in the first stage; (2) DNA pooling is used in the first stage. In this paper, we focus on the latter. Zuo et al. (2006) investigated statistical power of such a design, among other things, but the cost of the study was not taken into account. The purpose of this paper is to study the optimal design under the given overall cost. We investigate how to allocate the resources to the two stages. Note that in addition to the measurement errors associated with DNA pooling, genotyping errors are also unavoidable with individual genotyping. Therefore, we discuss the optimal design combining genotyping errors associated with individual genotyping. The joint statistical distributions of test statistics in the first and second stages are derived. For a fixed cost, our results show that the optimal design requires no additional samples in the second stage but only that the samples in the first stage be re-used. When the second stage uses an entirely independent sample, however, the optimal design under a given cost depends on the population allele frequency and allele frequency difference between the case and control groups. For the current genotyping costs, we can roughly allocate 1/3 to 1/2 of the total sample size to the first stage for screening. [source] | ||||||||||