Why do twins run in families? Scientists identify two common genes in mothers

Scientists have identified two genetic variants that increase the likelihood of a women giving birth to non-identical twins. While a range of factors have been previously found to explain why some mothers end up having twins, efforts to characterise the genes that contribute to this outcome have been limited.

This latest research, published in the journal Cell, increases scientists' understanding of how a mother's genes can lead to the birth of twins. The authors conducted a genome-wide association study, comparing the genome of non-identical twins' mothers to identify common genetic variants between them.

This study only focuses on non-identical twinning, also known as "dizygotic" twinning. These are twins that developed from two different eggs during pregnancy and may be of different sexes, with different genetic and physical characteristics − in other words, the twins are no more alike than normal siblings.

Female fertility and genes

The scientists collected data from three different twin registers from the Netherlands, Australia and Minnesota (USA). They analysed the information regarding mothers who had given birth spontaneously to non-identical twins − meaning no assisted reproductive technique was involved − and for whom genomic data was provided.

In total, the researchers examined the genes of 1,980 mothers of twins and compared them to the genes of 12,953 women who gave birth to one baby. This allowed them to identify two genetic similarities between the twins' mothers. Indeed, they discovered that a sequence variation of the FSHB and SMAD3 genes was often present, with the potential to increase the odds of non-identical twinning in women.

These two genes are directly involved in female fertility. The FHSB gene is responsible for producing higher levels of FSH, the hormone which stimulates egg maturation. The FHSB variant in mothers of twins may lead them to producing higher levels of FSH, increasing the probability of two eggs being released per cycle.

The second variant identified for gene SMAD3 may alter how receptive the ovaries are to FSH signalling. Mothers may not in this case display high levels of FSH, but their ovaries could be more sensitive to the hormone, also leading to the release of two eggs in a cycle.

Improving fertility treatments

The scientists say other genes may be involved in dizygotic twinning and should be identified in future research. However, they believe this study is a first step in better understanding the genetic differences between mothers of twins and mothers of a single child.

Beyond this discovery, their work also increases the knowledge of how ovaries and reproductive hormones function, opening up new possibilities for infertile women.

"This study provides important insights into ovarian functioning and the control of natural multiple follicle growth and reproductive ageing. This has important implications for fertility, including improved outcome prediction and novel avenues of fertility treatment," the scientists concluded.