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Using Network Methodology to Infer Population Substructure.

Prokopenko D, Hecker J, Silverman E, Nöthen MM, Schmid M, Lange C, Loehlein Fier H - PLoS ONE (2015)

Bottom Line: We group the sequenced individuals into triads, which depict the relational structure, on the basis of a predefined pairwise similarity measure.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genomic Mathematics, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.

ABSTRACT
One 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.

No MeSH data available.


Related in: MedlinePlus

3 African subpopulations.The polygons around the nodes represent the detected communities. The node colors represent the actual labels.
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pone.0130708.g002: 3 African subpopulations.The polygons around the nodes represent the detected communities. The node colors represent the actual labels.


Using Network Methodology to Infer Population Substructure.

Prokopenko D, Hecker J, Silverman E, Nöthen MM, Schmid M, Lange C, Loehlein Fier H - PLoS ONE (2015)

3 African subpopulations.The polygons around the nodes represent the detected communities. The node colors represent the actual labels.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4476755&req=5

pone.0130708.g002: 3 African subpopulations.The polygons around the nodes represent the detected communities. The node colors represent the actual labels.
Bottom Line: We group the sequenced individuals into triads, which depict the relational structure, on the basis of a predefined pairwise similarity measure.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genomic Mathematics, University of Bonn, Bonn, Germany; Institute of Human Genetics, University of Bonn, Bonn, Germany.

ABSTRACT
One 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.

No MeSH data available.


Related in: MedlinePlus