Tall story: Tiny gene variation influences height

By Agence France-Presse

PARIS–Scientists on Sunday announced they had uncovered the first gene that helps explain common differences in height among humans.

Just a single change in the gene’s DNA code determines whether people will be taller or shorter by up to one centimeter (0.4 of an inch), they said, adding that hundreds of other genes are also likely to play a role in height.

Genetic heritage has long been known as the driver of height — everyone knows that a child whose parents are both tall is also likely to grow up tall, too.

Unlike obesity, where genes and environmental factors (nutrition and exercise for example) play a joint role, around 90 percent of the determinants for height are genetic.

Even though the link is clearly there, finding “height” genes that are common across the population has been strangely elusive. Until now, the only evidence has been spotted among a small group of people with a rare condition that affects their stature.

In a paper published by the journal Nature Genetics, British and US sleuths analyzed DNA from nearly 5,000 white people of European descent, mainly individuals living in Britain, Sweden and Finland.

The exhaustive trawl threw up a gene called HMGA2.

The change of just a single base “letter” in HMGA2’s genetic code — a “C” (for cytosine) instead of a “T” (for thymine) — adds nearly a centimeter (0.4 of an inch) in height to individuals who inherited this variant from both parents.

Those who got the “C” variant from only one of their parents were about half a centimeter (0.2 of an inch) taller than their “T” counterparts.

After comparing this discovery to further studies of nearly 30,000 other people, the team believes around a quarter of white Europeans carry the double “C” variant. Around a quarter have the double “T” version, thus leaving them about a centimeter (0.4 inch) shorter than their double “C” counterparts.

Many more other genes remain to be uncovered, for HMGA2 explains only 0.3 percent of the variability in human stature.

“Height is a typical ‘polygenic’ trait, in other words many genes contribute towards making us taller or shorter,” said lead researcher Tim Frayling of the Peninsula Medical School in Exeter, southwestern England.

“Clearly, our results do not explain why one person will be six feet five inches (192 cms) and another only four feet 10 inches (145 cms). This is just the first of many that will be found, possibly as many as several hundred.”

Another step is to explain why HMGA2 has this effect. Researchers believe it plays a role in growth through regulating cell growth.

Interest in “height” genes is spurred by more than idle curiosity, for there could also be a windfall in knowledge about disease.

Taller people are statistically more likely to be at risk from some kinds of cancer (prostate, bladder and lung, for instance), which implies that genes that regulate cell multiplication may also play some part in letting cancer cells proliferate. Statistics also throw up an association between shortness and heart disease.

“This is the first convincing result that explains how DNA can affect normal variation in human height,” said US researcher Joel Hirschhorn of the Broad Institute, Massachusetts, and a professor of genetics at Harvard Medical School.

“Because height is a complex trait, involving a variety of genetic and non-genetic factors, it can teach us valuable lessons about the genetic framework of other complex traits, such as diabetes, cancer and other common human diseases.”

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