Population admixture

Whereas the impact of population admixture, or population stratification, to false positives in case-control studies is still under debate, every effort to minimize it should be taken. These efforts include the use of homogeneous populations or the use of family relatives as controls (e.g., siblings in case-sib studies). When these approaches are not possible, results should always be controlled for ethnicity. In 

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Deng, H.W., "Population Admixture May Appear to Mask, Change or Reverse Genetic Effects of Genes Underlying Complex Traits," Genetics, 159, 1319-1323 (2001). 

The alleles containing 4 and 9 copies of the TSER repeat were primarily confined to African populations. TSER 4 accounted for 2-7% of TSER alleles in all African populations except the Sudanese. However, TSER 4 was also found in a British Caucasian subject but not among the American-Caucasian population studied [53]. This suggests that TSER 4 occurs at a low frequency in Caucasian populations. The absence of the TSER 4 allele in the Sudanese population may be a result of the small sample size or due to the fact that this allele occurs at very low frequencies in this population. The latter possibility would make sense as this population is an admixture of Negroid and Caucasoid characteristics at both the morphological and molecular levels [17]. 

As populations amalgamate, opportunities for gene flow between the populations begin. This process of genetic admixture leads to considerations similar to those of population substructure. The difference is that with... 

Smith, M.W., et al., "Markers for Mapping by Admixture Linkage Disequilibrium in African American and Hispanic Populations," Am.. Hum. Genet., 69,1080-1094 (2001). 

Keywords Admixture association study confounding human genetics population structure. 

One major concern of the association study is that spurious associations may occur if the genetic background in cases is different from that in controls. Genetic heterogeneity in a population can be a result of population structure and recent admixture. In this chapter, we review the problem of population structure, demonstrate how that structure affects association study, and discuss solutions to this problem. 

Confounding is not a concern in TDT because the allelic transmission within families is unaffected by population structure and admixture. Information on hap-lotypes is available in family-based design and may help increase the test power. There are two major drawbacks in family-based design. First, if the disease occurs... 

Because of the difficulties in family-based design, an association study with a case-control design is more and more commonly used by investigators. Because of the concern of confounding caused by population structure and recent admixture, appropriate adjustment of stratification should be used in association studies. A number of approaches have been developed for this purpose. 

In addition to these three major methods mentioned, several other computational approaches can also be used to deal with population stratification. For example, ADMIXMAP (22-26) is a model-based method that estimates the individual history of admixture. It can be applied to an admixed population with two or more ancestral populations. It also tests the association of a trait with ancestry at a marker locus with control for population structure. Wu et al. developed a software package in R (PSMIX) for the inference of population stratification and admixture (27). PSMIX is based on the maximum likelihood method. It performs as well as model-based methods such as STRUCTURE and is more computationally efficient. 

Redden, D.T., and Allison, D.B. (2006) The effect of assortative mating upon genetic association studies spurious associations and population substructure in the absence of admixture. Behav. Genet. 36, 678-686. 

Mckeigue, P.M., Carpenter, J., Parra, E.J., and Shriver, M.D. (2000) Estimation of admixture and detection of linkage in admixed populations by a Bayesian approach application to African-American populations. Ann. Hum. Genet. 64, 171-186. 

The admixture of singly-excited configurations O, to Og to represent the HF wave function indicates electron transfer from bonding to antibonding orbitals and, accordingly, can be interpreted in terms of electron delocalization, which can be measured by the ratio CjlCG. Alternatively, one can define interbond populations by equation 1647 80 ... 

Eq. (8) then shows that the Kramers doublets will no longer correspond to almost pure -orbitals, but will contain appreciable admixtures of the other -orbitals if the tetragonal and rhombic splittings become considerably smaller than in the azides. Furthermore the population probability for the excited states would increase if the energy gaps between the three states became smaller (Fig. 24), and thermal mixing of the three Kramers doublets might then also have to be considered. 

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