Genomics

The long and the short of it

You can mainly blame — or thank — your genes for your height. But although an estimated 80% of the variability in height is thought to be down to genetic factors, pinpointing which genes are the main drivers is a challenge. Researchers of the GIANT Consortium now report the most comprehensive analysis yet of genomic factors that affect human height (H. Lango Allen et al. Nature doi:10.1038/nature09410; 2010).

Unlike features such as the ABO blood group, which are probably determined by single genes, height is a complex trait resulting from the cumulative — but individually small — contribution of many genes. So identifying small-effect genes requires studies with large sample sizes.

Lango Allen et al. performed a meta-analysis of data from other genome-wide association (GWA) studies, investigating variations in height in nearly 185,000 adults. Their paper, however, is notable not just for being one of the largest GWA studies to date, but also for identifying the largest number (180) of genomic loci associated with a single trait.

Credit: Courtesy Everett Collection/Rex Features

GWA studies are often criticized for providing data of little immediate significance. So what else can be deduced from the authors' findings? The 180 shortlisted loci are enriched in genes implicated in abnormal skeletal growth; such genes most often lie nearest to a height-associated variant. What's more, for five loci, height-linked variants correlated strongly with variants associated with traits and disorders such as bone mineral density, rheumatoid arthritis and obesity. One possibility is that the latter variants affect height indirectly. The authors argue, therefore, that one benefit of GWA studies is that they highlight genes deserving of further study.

But there is at least one more step to go. Variants at an estimated 517 other loci may make similar or greater contributions and, together with Lango Allen and colleagues' 180 loci, would account for some 20% of height heritability. To identify these additional loci, around 500,000 individuals must be sampled.

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Shadan, S. The long and the short of it. Nature 467, 539 (2010). https://doi.org/10.1038/467539a

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