Whenever I lecture about quantitative genetics, I always talk about height in humans as an example of a trait influenced by the expression of many genes. Since I teach at the University of Connecticut, I often show the pair of photographs in this article from Genetice1, because (a) it shows a nice bell curve of heights and (b) it allows me to show how the environment can influence the expression of quantitative traits.2 I talk about Nilsson-Ehle's results on kernel color in wheat as an example of how multiple genes3 may influence the expression of a phenotype.
Now thanks to recent work described in Nature Genetics I can give students a best guess as to how many genes influence height variation in humans. The answer?
Fifty-four
Genome-wide association studies have identified many variants affecting susceptibility to disease. Now, three studies use this approach to study adult height variation in a combined sample size of ~63,000 individuals and report a total of 54 validated variants influencing this trait.4,5,6,7
Height variation in humans is a nice example not only because its something students can easily relate to, but also because it's the classic trait that Francis Galton studied when he was trying to work out the principles of inheritance in the late 19th century. When plotting his data he noticed that offspring are, on average, closer to the mean height than the parents – they regress to the mean. The straight-line he fit (with Karl Pearson's help) to describe this relationship was called a regression line.
And that's where we get linear regression.
1Crow, J. F. 1997. Birth defects, jimson weed, and bell curves. Genetics 147:1-6.
2Strictly speaking, of course, the pair of photographs shows no such thing, but because there were only a few human generations between 1917 and 1996 and because we know from other evidence that nutrition and health affect stature, it seems reasonable to conclude that the difference in means reflects improvements in nutrition and health in the United States over the 20th century.
3In that case three.
4Visscher, P.M. (2008). Sizing up human height variation. Nature Genetics, 40(5), 489-490. DOI: 10.1038/ng0508-489
5Weedon, M.N., Lango, H., Lindgren, C.M., Wallace, C., Evans, D.M., Mangino, M., Freathy, R.M., Perry, J.R., Stevens, S., Hall, A.S., Samani, N.J., Shields, B., Prokopenko, I., Farrall, M., Dominiczak, A., Johnson, T., Bergmann, S., Beckmann, J.S., Vollenweider, P., Waterworth, D.M., Mooser, V., Palmer, C.N., Morris, A.D., Ouwehand, W.H., Zhao, J.H., Li, S., Loos, R.J., Barroso, I., Deloukas, P., Sandhu, M.S., Wheeler, E., Soranzo, N., Inouye, M., Wareham, N.J., Caulfield, M., Munroe, P.B., Hattersley, A.T., McCarthy, M.I., Frayling, T.M. (2008). Genome-wide association analysis identifies 20 loci that influence adult height. Nature Genetics, 40(5), 575-583. DOI: 10.1038/ng.121
6Lettre, G., Jackson, A.U., Gieger, C., Schumacher, F.R., Berndt, S.I., Sanna, S., Eyheramendy, S., Voight, B.F., Butler, J.L., Guiducci, C., Illig, T., Hackett, R., Heid, I.M., Jacobs, K.B., Lyssenko, V., Uda, M., Boehnke, M., Chanock, S.J., Groop, L.C., Hu, F.B., Isomaa, B., Kraft, P., Peltonen, L., Salomaa, V., Schlessinger, D., Hunter, D.J., Hayes, R.B., Abecasis, G.R., Wichmann, H., Mohlke, K.L., Hirschhorn, J.N. (2008). Identification of ten loci associated with height highlights new biological pathways in human growth. Nature Genetics, 40(5), 584-591. DOI: 10.1038/ng.125
7Gudbjartsson, D.F., Walters, G.B., Thorleifsson, G., Stefansson, H., Halldorsson, B.V., Zusmanovich, P., Sulem, P., Thorlacius, S., Gylfason, A., Steinberg, S., Helgadottir, A., Ingason, A., Steinthorsdottir, V., Olafsdottir, E.J., Olafsdottir, G.H., Jonsson, T., Borch-Johnsen, K., Hansen, T., Andersen, G., Jorgensen, T., Pedersen, O., Aben, K.K., Witjes, J.A., Swinkels, D.W., Heijer, M.d., Franke, B., Verbeek, A.L., Becker, D.M., Yanek, L.R., Becker, L.C., Tryggvadottir, L., Rafnar, T., Gulcher, J., Kiemeney, L.A., Kong, A., Thorsteinsdottir, U., Stefansson, K. (2008). Many sequence variants affecting diversity of adult human height. Nature Genetics, 40(5), 609-615. DOI: 10.1038/ng.122
Did you see the tiny effect size? They account for maybe 2-4% of the variation in adult human height, and that is using 20+ loci. Not to mention the 2 dozen or though authors on each paper, means a LOT of effort to explain very little about a trait that doesn't matter much (until you get to the extremes).
I did take a lot of effort (about $30 million according to Visscher). If the studies had been done only for this purpose, I might agree that it's a lot of effort chasing a hypothesis where we already knew the basic answer -- Lots of genes influence height variation in humans. I found the studies interesting mostly because it puts a number on "lots" and because it shows the types of analyses that are possible given the wealth of genetic data now available in human populations.