The genetics of height is incredibly complex. Though height is strongly determined by genetics, no single gene appears to have much influence over how tall a person will be. Instead, there appear to be dozens of genetic variants involved, none of which account for more than a few millimeters’ height difference.
It will be no small feat for geneticists to identify all of the genetic contributors to height and out how they work together. But by analyzing growth data for a group of 3,538 people who were born in northern Finland in 1966, an international group of researchers has taken a step in that direction by figuring out when a few height-related genes exert their effects. They describe their research in the March issue of PLoS Genetics.
Humans tend to do most of their growing in two spurts, once during infancy and then again around the onset of puberty. Growth during infancy tends to be associated with how much nutrition a child absorbs, whereas the second growth spurt is governed more by hormonal signals. So it would not be surprising to find that different sets of genes are associated with growth during the two periods.
The researchers tested that theory by selecting 48 SNPs that have been associated with adult height in previous studies. Then they looked at growth data for each subject from birth to age 20 to determine whether any of those SNPs was associated with growth during infancy, around puberty or both.
Five SNPs were significantly associated with growth during infancy, and seven with the puberty-associated growth spurt. Only one was associated with growth during both periods.
The researchers were especially interested in two SNPs. One was in the gene SOCS2, which influences growth hormone signaling, and was associated with growth during puberty. The other was in the gene HHIP, which is involved in embryogenesis and development, and was associated with growth during infancy.
(23andMe customers can check their genotype for both of these SNPs using the Genome Browser. Each T version of the SOCS2 SNP was associated with faster growth during infancy, and 4.7 mm of adult height. Each A version of the HHIP SNP was associated with faster growth around the time of puberty, but was not significantly related to adult height.)
This research illustrates the value of collecting data over time in genetic association studies. Knowing not just whether, but when, a particular genetic variation exerts its effects can provide vital clues to how it works.