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 language | English |
|---|---|
| Article number | e29475 |
| Journal | PLoS ONE |
| Volume | 6 |
| Issue number | 12 |
| DOIs | |
| State | Published - 27 Dec 2011 |
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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 journal › Article
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.
UR - http://www.scopus.com/inward/record.url?scp=84455192452&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0029475
DO - 10.1371/journal.pone.0029475
M3 - Article
C2 - 22216288
AN - SCOPUS:84455192452
VL - 6
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 12
M1 - e29475
ER -