Extent of height variability explained by known height-associated genetic variants in an isolated population of the Adriatic coast of Croatia.
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.


RESULTS
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
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.
Human Genetics Division, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Ge
G
Zhang
Rebekah
R
Karns
Guangyun
G
Sun
Subba Rao
SR
Indugula
Hong
H
Cheng
Dubravka
D
Havas-Augustin
Natalija
N
Novokmet
Dusko
D
Rudan
Zijad
Z
Durakovic
Sasa
S
Missoni
Ranajit
R
Chakraborty
Pavao
P
Rudan
Ranjan
R
Deka
D001827:Body Height / Q000235:genetics*; D017523:Croatia; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D020641:Polymorphism, Single Nucleotide