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Selection Shaped Genetic Differences in Height, BMI Among European Populations

NEW YORK (GenomeWeb) – Differences in height and body mass index among European populations can be traced to many independent genetic loci, according to a new study from a University of Queensland-led team of researchers.

By drawing on data from more than 250,000 European individuals and effect size estimates from some 17,500 sibling pairs, researchers led by Queensland's Peter Visscher calculated the population genetic variance for height and BMI, as the investigators reported in Nature Genetics today. Selection, they added, appears to have driven the differences seen among the populations, with northern Europeans generally being taller and more slender than southern Europeans.

"Our findings give a genetic basis to the stereotype of Scandinavians as being tall and lean," first author Matthew Robinson from the Queensland Brain Institute said in a statement.

Using population genetic analyses, the researchers estimated the cumulative population genetic differentiation for height and BMI, as captured by unlinked loci, in more than 9,400 Europeans from 14 countries.

They first performed a genome-wide association study meta-analysis to uncover independent loci linked to either height or BMI. After re-estimating the effects of each SNP, using a within-family study design, the researchers developed genetic predictors for both phenotypes from those new effect sizes. Through a Bayesian mixed-model approach, they estimated the proportion of variance in the genetic predictors that could be chalked up to population differences.

Up to 24 percent and 8 percent of variance in the polygene predictors could be attributed to population genetic differences in height and BMI, respectively, the researchers reported.

Both height and BMI diverged among the populations more than would be expected under a neutral model of random chance. Instead, Visscher and his colleagues said their results indicate that these differences in population genetics for height and BMI have been driven by selection.

Selection, they added, appears to have acted on both phenotypes. At the population level, a genetic predisposition for being tall was associated with a genetic predisposition for being slender. But as some genes influence both height and BMI, the researchers couldn't rule out that differentiation seen in one trait was mediated by selection on the other.

They also noted a strong association between predicted population genetic means  and observed height patterns. This indicated to them that the phenotypic differences they observed across European countries reflected differences in allele frequencies at common height-linked loci.

However, the observed BMI patterns didn't reflect the pattern of population genetic differentiation. Instead, the researchers suggested that environmental differences among European countries — such as diet, economy, and climate — might mask the population genetic differentiation.

"This suggests that differences in diet, for example, are more important than genetics in creating differences in BMI among nations," Robinson said.

Overall, this approach could be applied to examine population differences in a range of phenotypes, the researchers noted, including conditions like dementia, diabetes, and heart disease.

"Countries' populations differ in many ways, from the height of their people to the prevalence of certain diseases," Robinson added.