Your Height Genes Have Second Jobs: Meet GDF5 and EFEMP1

You know your height. It is on your passport, it was pencilled on a door frame when you were seven, and you have probably added a centimetre to it at least once. Of everything written in your DNA, it feels like the simplest: some people got the tall genes and some did not.

Except that there is no such thing as a gene that only does height. This week this site wrote pages on two conditions that have nothing to do with how tall you are — worn knees and groin hernias — and the same positions kept turning up.

A fifth of the genome

Start with how much of you is involved. Yengo et al. 2022 measured height against the DNA of 5.4 million people and found 12,111 independent positions that matter. They sit in 7,209 stretches of the genome which, added together, cover about 21% of it.

When a fifth of the genome has a hand in one trait, those stretches cannot be reserved for that trait. The genes inside them build bone, cartilage and the tissue that holds organs in place. Height is one of the things that comes out. It is not the only one.

GDF5: taller, and easier on the knee

rs224333 sits in GDF5, a growth factor that helps form joints. On this site it is filed under height: in the GWAS Catalog's records, one version of it goes with being taller in several studies, among them one of 153,950 Korean adults.

The largest study of osteoarthritis, in 1,962,069 people, reports the same position — and the same version. People who carry it have lower odds of knee osteoarthritis: an odds ratio of 0.94. One stretch of DNA, a little more height, a little less wear in the knee.

EFEMP1: taller, and harder on the groin

Now the other direction. rs1346786 sits in EFEMP1, and it too is filed here under height: in the 5.4 million study, one version goes with being taller. A UK Biobank study reports that same version with higher odds of inguinal hernia — an odds ratio of 1.19.

That is less strange than it sounds. EFEMP1 was one of four genes named by the first genetic study of hernia, in 2015, because of its part in maintaining connective tissue — the material that gives the body its frame and also holds the abdominal wall shut.

So is tall good or bad?

Neither, and that is the point. Two positions, both with a taller version, and one goes with better knees while the other goes with more hernias. These are effects of particular stretches of DNA, not of height. Nobody's knee is protected by being tall, and nobody gets a hernia from it.

Geneticists call this pleiotropy: one stretch of DNA, more than one effect. It is not limited to height. rs1421085 in FTO is filed on this site under obesity, and the version that goes with lower body mass index also goes with lower odds of a hip or knee replacement for osteoarthritis, an odds ratio of 0.94.

Where this touches this site

Of the 62 positions on this site's osteoarthritis page, 51 were already in the catalogue under another trait before the osteoarthritis study reported them. The bones topic collects the pages, and the Gene Knowledge Graph shows each gene with every condition it reaches.

So the mark on the door frame was never the whole story. The DNA that set it was busy with your knees and the wall of your abdomen as well.