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000137987 0247_ $$2doi$$a10.1371/journal.pone.0130708
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000137987 041__ $$aEnglish
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000137987 1001_ $$aProkopenko, Dmitry$$b0
000137987 245__ $$aUsing Network Methodology to Infer Population Substructure.
000137987 260__ $$aSan Francisco, California, US$$bPLOS$$c2015
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000137987 520__ $$aOne of the main caveats of association studies is the possible affection by bias due to population stratification. Existing methods rely on model-based approaches like structure and ADMIXTURE or on principal component analysis like EIGENSTRAT. Here we provide a novel visualization technique and describe the problem of population substructure from a graph-theoretical point of view. We group the sequenced individuals into triads, which depict the relational structure, on the basis of a predefined pairwise similarity measure. We then merge the triads into a network and apply community detection algorithms in order to identify homogeneous subgroups or communities, which can further be incorporated as covariates into logistic regression. We apply our method to populations from different continents in the 1000 Genomes Project and evaluate the type 1 error based on the empirical p-values. The application to 1000 Genomes data suggests that the network approach provides a very fine resolution of the underlying ancestral population structure. Besides we show in simulations, that in the presence of discrete population structures, our developed approach maintains the type 1 error more precisely than existing approaches.
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000137987 650_2 $$2MeSH$$aAlgorithms
000137987 650_2 $$2MeSH$$aHumans
000137987 650_2 $$2MeSH$$aModels, Genetic
000137987 650_2 $$2MeSH$$aPolymorphism, Single Nucleotide
000137987 650_2 $$2MeSH$$aPopulation: genetics
000137987 7001_ $$aHecker, Julian$$b1
000137987 7001_ $$aSilverman, Edwin$$b2
000137987 7001_ $$0P:(DE-HGF)0$$aNöthen, Markus M$$b3
000137987 7001_ $$0P:(DE-HGF)0$$aSchmid, Matthias$$b4
000137987 7001_ $$0P:(DE-2719)9000181$$aLange, Christoph$$b5$$udzne
000137987 7001_ $$aLoehlein Fier, Heide$$b6
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