A new genome-wide association study has yielded two more genes associated with height. But just like the amount of height difference the new genes explain, their discovery amounts to no more than an inch of progress in understanding the genetics of the trait.
Height is one of the most genetically complex traits scientists face. There are probably hundreds of different genes that influence stature, with each one accounting for only a tiny fraction of the difference in height from one person to the next. And though genes are by far the most important determinant of height, all other things being equal, all other things are by no means equal. Differences in childhood nutrition, prenatal care and infection history can cause even identical twins can to reach very different heights (more on that here).
Discerning the effect of a single genetic variation in such a noisy environment requires multiple studies involving large numbers of subjects. The latest study, published online last week by Human Molecular Genetics, looked at 379,319 SNPs in 1,000 people of European descent.
The study found statistically significant associations with height for 134 SNPs. The researchers focused on about two dozen that clustered around two genes that had not previously been associated with height, SBF2 and FLNB.
FLNB is plausible as a height-associated gene, because it is involved in skeletal development. Though SBF2 is not as clearly related to height, mutations in the gene are known to cause Charcot-Marie-Tooth disease, which causes muscle weakness and skeletal deformities in the limbs.
The effect of SBF2 was surprisingly large – subjects with the TT genotype at one SNP in the gene, rs1867138, were about an inch taller on average than those with the CC genotype. Though the effect of FLNB was less impressive, the study found that each G at the the SNP rs9834312 in that gene slightly increased a subject’s height.
23andMe customers can check their genotypes at two equivalent SNPs using the Browse Raw Data feature. Having a G at rs1867137 is the same as having a T at rs1867138. So the GG genotype at rs1867137 is worth about an inch compared to AA. In FLNB, rs939882 is equivalent to rs9834312. In both cases, having a G is correlated with slightly greater height.
When the researchers attempted to replicate their findings in Chinese subjects, they found that both genes were associated with height in that population as well – but not all of it. The SNP in FLNB was associated with height among 619 northern Chinese subjects, while the SNP in SBF2 was associated with height only in a sample of 2,953 southern Chinese.
But when the researchers tried to replicate previously discovered height associations using their data, their results were mixed. Out of 58 they looked for, only 13 showed up. That doesn’t necessarily mean the 45 associations that could not be replicated are invalid; but it does illustrate how difficult it will be to work out the genetic basis of height.