Because genome-wide association studies (GWAS) are being performed with larger and larger numbers of individuals (cohorts), increasing numbers of small-effect genes (genotype) are becoming identified. Each of these genes are associated (statistically significantly) with the trait (phenotype) of “height.” At latest count, ~700 genes have been associated with height –– but virtually all of them are small-effect genes, which means that (individually) each gene contributes an almost imperceptibly small difference (i.e. a millimeter, or less). The people of Peru are one of the world’s shortest populations. As described in the [attached] 2-page editorial, a group studying the genetics of Peruvians has discovered a DNA variant in one gene that, amazingly, affects a person’s height by more than 2 centimeters, on average.
One important aspect of this particular study is that the scientists have looked at an isolated population, i.e. those living at high altitude in Peru. It appears that this gene variant is not known outside Peru, where the “selective pressure of living at high altitude” is likely to have driven its evolution. Authors of this genetics group collected genetic information from 4,002 Peruvians, along with other data including height. Peruvian men average 165 centimeters, women about 153 centimeters — in both cases, these are ~10 centimeters shorter than average people in the U.S.
The team decided to search Peruvian DNA for genetic factors underlying this short stature, comparing the genomes of Peruvians with those of Africans, Europeans, and Native Americans. (Peruvians are about 80% Native American, 16% European, and 3% African.) The shortest Peruvians carry a variant (allele), of a gene called FBN1 (fibrillin-1) that differs by one nucleotide base from the gene’s usual DNA sequence. This mutated variant alters one amino acid in fibrillin-1, a carbohydrate-coated protein that provides structural support in connective tissue.
Interestingly, virtually all of the ~700 genes associated (worldwide) with the trait of height, with their individually small effects, together explain only ~7% height (variance explained). This newly discovered Peruvian variant, alone –– accounts for another 1% –– all by itself..!! A person carrying just one copy of this FBN1 variant is about 2.2 centimeters shorter than people with consensus (wild-type) alleles of the gene. Peruvians having two copies of this FBN1 variant are usually more than 4 centimeters shorter.
Science 18 May 2o18; 360: pp 696–697 [editorial]