Why Do Fraternal Twins Run in Families?

Why do fraternal twins (twins who develop in two separate eggs) seem to run in families? It’s all about genes. A team of researchers say they’ve identified two genes associated with giving birth to twins, and their results are published in the American Journal of Human Genetics. 

Twin births are on the rise in America. In 1980, one in every 53 babies was a twin. By 2009, that number was one in 30. In almost every state (and D.C.), the rate of twin births has increased by more than 50 percent in the last three decades.

What’s causing it? It’s complicated. Fertility treatments, which often result in multiple births, are definitely on the rise. But parenthood is changing in other ways. Fraternal, or dizygotic (DZ) twin births are more likely in women with a higher body mass index (BMI), as well as mothers over the age of 40—two demographics that have increased since the 1980s. And then there’s another element: Many of these DZ twins are born to women who are related to one another.

Researchers therefore believed there must be a genetic component to twinning, yet previous searches for a DZ-twinning gene had been unsuccessful. So rather than look for a twinning gene specifically, an international team of scientists combed through the genomes of women both with and without DZ twins, looking for commonalities.

They began by compiling data from genetic databases in three countries: the Netherlands Twin Register and the Netherlands Study of Depression and Anxiety; the Australian Twin Registry; and a study from the Minnesota Center for Twin and Family Research. All told, the researchers were working with genetic information from 1980 mothers of DZ twins and 12,953 more control subjects. They conducted a sweep of all the subjects’ genomes, which yielded three gene variants that seemed more common in women who had DZ twins.

The team then sent that data to researchers in Iceland. Analysts there scanned the genomes of another 3597 mothers with twins and 297,348 controls, looking for the variants the original team had identified.

Two of the three variants reappeared with some frequency in the Icelandic group of mothers of DZ twins. One variant is associated with follicle-stimulating hormone (FSH), a hormone that causes growth in a woman’s ovaries. Women with this variant tend to make more FSH than others. When ovaries grow quickly, they release eggs more quickly, which could lead to the release of multiple eggs at one time. And if multiple eggs are fertilized, they could lead to multiple babies. Women with this variant were 18 percent more likely than others to have twins.

The other variant lives in a gene called SMAD3, which influences how cells communicate with one another. The researchers think this variant may increase a woman’s sensitivity to FSH, so that even a normal amount of FSH could trigger the release of multiple eggs. Having the SMAD3 variant raised a woman’s relative risk of twins by 9 percent. Having both variants pushed the odds to 29 percent. (The researchers called it a "risk" because, as they note, having twins can be risky for the health of mothers and babies.)

Image Credit: Hamdi Mbarek

These two variants are probably just two of many, the researchers say. "There is a very clear suggestion and indication that more loci are contributing to the risk of having dizygotic twins as well," Dorret Boomsma, a biological psychologist at Vrije Universiteit (VU) Amsterdam, said in a press statement. "We've characterized the first two that have been replicated."