TY - JOUR
T1 - Population structure, migration, and diversifying selection in the Netherlands
AU - Abdellaoui, Abdel
AU - Hottenga, Jouke-Jan
AU - Knijff, Peter De
AU - Nivard, Michel G.
AU - Xiao, Xiangjun
AU - Scheet, Paul
AU - Brooks, Andrew
AU - Ehli, Erik A.
AU - Hu, Yueshan
AU - Davies, Gareth E.
AU - Hudziak, James J.
AU - Sullivan, Patrick F.
AU - van Beijsterveldt, Toos
AU - Willemsen, Gonneke
AU - de Geus, Eco J.
AU - Penninx, Brenda W. J. H.
AU - Boomsma, Dorret I.
AU - van Beijsterveldt, C.E.M.
PY - 2013/11
Y1 - 2013/11
N2 - Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North-South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs-the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. © 2013 Macmillan Publishers Limited.
AB - Genetic variation in a population can be summarized through principal component analysis (PCA) on genome-wide data. PCs derived from such analyses are valuable for genetic association studies, where they can correct for population stratification. We investigated how to capture the genetic population structure in a well-characterized sample from the Netherlands and in a worldwide data set and examined whether (1) removing long-range linkage disequilibrium (LD) regions and LD-based SNP pruning significantly improves correlations between PCs and geography and (2) whether genetic differentiation may have been influenced by migration and/or selection. In the Netherlands, three PCs showed significant correlations with geography, distinguishing between: (1) North and South; (2) East and West; and (3) the middle-band and the rest of the country. The third PC only emerged with minimized LD, which also significantly increased correlations with geography for the other two PCs. In addition to geography, the Dutch North-South PC showed correlations with genome-wide homozygosity (r=0.245), which may reflect a serial-founder effect due to northwards migration, and also with height (♂: r=0.142, ♀: r=0.153). The divergence between subpopulations identified by PCs is partly driven by selection pressures. The first three PCs showed significant signals for diversifying selection (545 SNPs-the majority within 184 genes). The strongest signal was observed between North and South for the functional SNP in HERC2 that determines human blue/brown eye color. Thus, this study demonstrates how to increase ancestry signals in a relatively homogeneous population and how those signals can reveal evolutionary history. © 2013 Macmillan Publishers Limited.
KW - Confidence Intervals
KW - Genealogy and Heraldry
KW - Genetic Variation/genetics
KW - Genetics, Population
KW - Genome, Human/genetics
KW - Genome-Wide Association Study
KW - Geography
KW - Haplotypes/genetics
KW - Human Migration
KW - Humans
KW - Linkage Disequilibrium/genetics
KW - Netherlands
KW - Polymorphism, Single Nucleotide/genetics
KW - Principal Component Analysis
KW - Selection, Genetic
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84885938427&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/23531865
U2 - https://doi.org/10.1038/ejhg.2013.48
DO - https://doi.org/10.1038/ejhg.2013.48
M3 - Article
C2 - 23531865
SN - 1018-4813
VL - 21
SP - 1277
EP - 1285
JO - European journal of human genetics
JF - European journal of human genetics
IS - 11
ER -