Extent of height variability explained by known Height-Associated genetic variants in an isolated population of the Adriatic Coast of Croatia

Ge Zhang, Rebekah Karns, Guangyun Sun, Subba Rao Indugula, Hong Cheng, Dubravka Havas-Augustin, Natalija Novokmet, Dusko Rudan, Zijad Durakovic, Sasa Missoni, Ranajit Chakraborty, Pavao Rudan, Ranjan Deka

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Background: Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2~10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. Methodology/Principal Findings: In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. Conclusions/Significance: We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.

Original languageEnglish
Article numbere29475
JournalPLoS ONE
Volume6
Issue number12
DOIs
StatePublished - 27 Dec 2011

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Croatia
Coastal zones
Genes
Single Nucleotide Polymorphism
Genome-Wide Association Study
coasts
Population
loci
Multifactorial Inheritance
Islands
Genome
quantitative traits
phenotypic variation
genetic background
sampling
genome

Cite this

Zhang, Ge ; Karns, Rebekah ; Sun, Guangyun ; Indugula, Subba Rao ; Cheng, Hong ; Havas-Augustin, Dubravka ; Novokmet, Natalija ; Rudan, Dusko ; Durakovic, Zijad ; Missoni, Sasa ; Chakraborty, Ranajit ; Rudan, Pavao ; Deka, Ranjan. / Extent of height variability explained by known Height-Associated genetic variants in an isolated population of the Adriatic Coast of Croatia. In: PLoS ONE. 2011 ; Vol. 6, No. 12.
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title = "Extent of height variability explained by known Height-Associated genetic variants in an isolated population of the Adriatic Coast of Croatia",
abstract = "Background: Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2~10{\%} of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. Methodology/Principal Findings: In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94{\%} of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5{\%} of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. Conclusions/Significance: We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.",
author = "Ge Zhang and Rebekah Karns and Guangyun Sun and Indugula, {Subba Rao} and Hong Cheng and Dubravka Havas-Augustin and Natalija Novokmet and Dusko Rudan and Zijad Durakovic and Sasa Missoni and Ranajit Chakraborty and Pavao Rudan and Ranjan Deka",
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Zhang, G, Karns, R, Sun, G, Indugula, SR, Cheng, H, Havas-Augustin, D, Novokmet, N, Rudan, D, Durakovic, Z, Missoni, S, Chakraborty, R, Rudan, P & Deka, R 2011, 'Extent of height variability explained by known Height-Associated genetic variants in an isolated population of the Adriatic Coast of Croatia', PLoS ONE, vol. 6, no. 12, e29475. https://doi.org/10.1371/journal.pone.0029475

Extent of height variability explained by known Height-Associated genetic variants in an isolated population of the Adriatic Coast of Croatia. / Zhang, Ge; Karns, Rebekah; Sun, Guangyun; Indugula, Subba Rao; Cheng, Hong; Havas-Augustin, Dubravka; Novokmet, Natalija; Rudan, Dusko; Durakovic, Zijad; Missoni, Sasa; Chakraborty, Ranajit; Rudan, Pavao; Deka, Ranjan.

In: PLoS ONE, Vol. 6, No. 12, e29475, 27.12.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Extent of height variability explained by known Height-Associated genetic variants in an isolated population of the Adriatic Coast of Croatia

AU - Zhang, Ge

AU - Karns, Rebekah

AU - Sun, Guangyun

AU - Indugula, Subba Rao

AU - Cheng, Hong

AU - Havas-Augustin, Dubravka

AU - Novokmet, Natalija

AU - Rudan, Dusko

AU - Durakovic, Zijad

AU - Missoni, Sasa

AU - Chakraborty, Ranajit

AU - Rudan, Pavao

AU - Deka, Ranjan

PY - 2011/12/27

Y1 - 2011/12/27

N2 - Background: Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2~10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. Methodology/Principal Findings: In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. Conclusions/Significance: We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.

AB - Background: Human height is a classical example of a polygenic quantitative trait. Recent large-scale genome-wide association studies (GWAS) have identified more than 200 height-associated loci, though these variants explain only 2~10% of overall variability of normal height. The objective of this study was to investigate the variance explained by these loci in a relatively isolated population of European descent with limited admixture and homogeneous genetic background from the Adriatic coast of Croatia. Methodology/Principal Findings: In a sample of 1304 individuals from the island population of Hvar, Croatia, we performed genome-wide SNP typing and assessed the variance explained by genetic scores constructed from different panels of height-associated SNPs extracted from five published studies. The combined information of the 180 SNPs reported by Lango Allen el al. explained 7.94% of phenotypic variation in our sample. Genetic scores based on 20~50 SNPs reported by the remaining individual GWA studies explained 3~5% of height variance. These percentages of variance explained were within ranges comparable to the original studies and heterogeneity tests did not detect significant differences in effect size estimates between our study and the original reports, if the estimates were obtained from populations of European descent. Conclusions/Significance: We have evaluated the portability of height-associated loci and the overall fitting of estimated effect sizes reported in large cohorts to an isolated population. We found proportions of explained height variability were comparable to multiple reference GWAS in cohorts of European descent. These results indicate similar genetic architecture and comparable effect sizes of height loci among populations of European descent.

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