the long and short of it

Height in humans turns out to be interesting to study. It is easily measured, but is influenced by genetic and environmental factors. Most of the variation is genetic, but is far from trivial - a few years ago some convincing evidence was found looking for single-letter differences — single nucleotide polymorphisms, or SNPs — in the genetic code that occur more often in taller people compared to shorter people. (' first heard this on a Quirks and Quarks program). The scan zeroed in on a single-letter difference, either a ‘C’ or ‘T’, in the HMGA2 gene that accounted for an estimated 0.3% of the height variation among study participants. Compared to individuals with two ‘T’-containing copies of the gene, those with one ‘C’-containing copy of the gene tended to be taller by about half a centimeter, and those with two copies were nearly a centimeter taller. It only accounted for a small percentage of observed variation in the population, but more work has been done.

Now something like a few dozen SNPs have been identified accounting for a few percent of the difference. Lots of work to do, but an interesting technique that requires a large number of measurements.

The link and abstract

Nat Genet. 2008 May;40(5):575-83. Epub 2008 Apr 6.

Genome-wide association analysis identifies 20 loci that influence adult height.

Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, Freathy RM, Perry JR, Stevens S, Hall AS, Samani NJ, Shields B, Prokopenko I, Farrall M, Dominiczak A; Diabetes Genetics Initiative; Wellcome Trust Case Control Consortium, Johnson T, Bergmann S, Beckmann JS, Vollenweider P, Waterworth DM, Mooser V, Palmer CN, Morris AD, Ouwehand WH; Cambridge GEM Consortium, Zhao JH, Li S, Loos RJ, Barroso I, Deloukas P, Sandhu MS, Wheeler E, Soranzo N, Inouye M, Wareham NJ, Caulfield M, Munroe PB, Hattersley AT, McCarthy MI, Frayling TM.
Genetics of Complex Traits, Institute of Biomedical and Clinical Science, Peninsula Medical School, Magdalen Road, Exeter EX1 2LU, UK.

Adult height is a model polygenic trait, but there has been limited success in identifying the genes underlying its normal variation. To identify genetic variants influencing adult human height, we used genome-wide association data from 13,665 individuals and genotyped 39 variants in an additional 16,482 samples. We identified 20 variants associated with adult height (P < 5 x 10(-7), with 10 reaching P < 1 x 10(-10)). Combined, the 20 SNPs explain approximately 3% of height variation, with a approximately 5 cm difference between the 6.2% of people with 17 or fewer 'tall' alleles compared to the 5.5% with 27 or more 'tall' alleles. The loci we identified implicate genes in Hedgehog signaling (IHH, HHIP, PTCH1), extracellular matrix (EFEMP1, ADAMTSL3, ACAN) and cancer (CDK6, HMGA2, DLEU7) pathways, and provide new insights into human growth and developmental processes. Finally, our results provide insights into the genetic architecture of a classic quantitative trait.