Abstract
BackgroundHuman 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 FindingsIn 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/SignificanceWe 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.
Highlights
Heritability of normal variation in human height is estimated to be,80%–90% [1,2,3,4], much of which is attributed to inherited factors [5]
We presented an estimation of variance explained by previously reported height-associated loci in a relatively isolated population based on a genome-wide scan of 2.5 M genotyped and imputed single nucleotide polymorphisms (SNPs) in 1304 individuals
We evaluated the percentage of variance explained by genetic scores based on previously reported panels of height-associated SNPs and their effect size estimates
Summary
Heritability of normal variation in human height is estimated to be ,80%–90% [1,2,3,4], much of which is attributed to inherited factors [5]. We have assessed the variance explained by known height-associated loci in a relatively isolated island population from the Adriatic coast of Croatia with limited admixture and homogeneous genetic background. We conducted a GWAS using a panel of 500K SNPs in a sample of .1300 adults to identify height-associated variants and estimated variance explained using genetic scores that combine information from panels of known loci from published. 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.
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