Genes behind increased chance of having non-identical twins identified.

By Dani Cooper

The first genetic clues as to why non-identical twins run in families have been revealed.

Key points

  • Non-identical twins run in families, but genes behind this have been a mystery
  • Analysis of large international databases of twins identifies two common genetic variants
  • Presence of both variants increases chance of twin birth by 29 per cent
  • Genes also have implications for fertility treatments

An international team of researchers from Europe, the US and Australia has identified two genes that increase the chances of mothers having non-identical — or dizygotic — twins.

The findings, published today in the American Journal of Human Genetics, may help in understanding better infertility issues in women and developing new treatments.

Co-author Professor Nick Martin, of the QIMR Berghofer Medical Research Institute, said while identical twinning was a random event that occurred about four in every 1,000 births across the globe, it “varied hugely between races”.

This ranged from two per 1,000 births in East Asians, to about 20 per 1,000 in West Africans with Europeans in the middle at eight per 1,000 births.

Fellow Australian co-author Dr Allan McRae, at the Queensland Brain Institute, said the study aimed to identify the genes common to women who had identical twins and get a better understanding of the mechanisms behind the hereditary trait.

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The researchers analysed the genetic information of 1,980 mothers of twins and 12,953 control subjects who did not have twins.

The information came from twin databases from the Netherlands, Minnesota and Australia, with the Australian sample including 606 mothers of twins and 6,656 control participants from the QIMR Berghofer Medical Research Institute twin study.

From that analysis the researchers identified a number of possible candidate genes.

These were then compared with genetic data from Iceland’s nationwide geneaological database that includes 3,597 mothers with twins and almost 300,000 control subjects.

Genes related to egg stimulating hormones

Professor Martin said two of the genes that had been identified in the three-country database search were also replicated in the Icelandic group.

This included a variant of the gene FSHB which encodes part of the follicle stimulating hormone (FSH) that is released from the pituitary gland.

Dr McRae said an increase in follicle stimulating hormone led to a higher chance of twin births because it increased the number of eggs that were released in the ovaries.

Identical vs non-identical twins

  • About 1 in 80 births in Australia is a twin and of these about 70 per cent are non-identical
  • Non-identical, or dizygotic, twins develop from two separate eggs from separate follicles fertilised by separate sperm cells whereas identical twins develop from one embryo that splits in half
  • Non-identical twins are as genetically alike to each other as any other sibling
  • Non-identical female twins are twice as likely as women in the general population to have twins themselves
  • Male non-identical twins can pass the genetic variants linked to twinning on to their daughters, thus explaining the myth that it skips a generation

“If there happens to be two eggs released at the right time it ends up with both eggs being fertilised,” he said.

The gene FSHB was also associated with an earlier age of menstruation, earlier age of first child and increased number of children among the cohort.

The second genetic variant was in the SMAD3 gene, which is involved in cell signalling in the ovaries.

Dr McRae said more work was needed in understanding the role of the SMAD3 variant but it was thought it might create a “more favourable environment for maturation of the egg”.

The study showed the FSHB variant increased the chance of having twins by 18 per cent, and SMAD3 by 9 per cent.

If a mother had both variants her chances of a twin birth was increased by 29 per cent.

Professor Martin said the latest study had identified other likely genes connected with identical twinning, but these findings were not replicated in the Icelandic cohort.

This may be because the Icelandic cohort included mothers who had used IVF treatment, whereas these women were screened out of the other twin databases.

Larger studies could also identify other genetic variants involved in the birth of non-identical twins.

‘Exciting’ implications for fertility treatments

Professor Martin said the findings were “an extremely exciting story” that had implications for fertility treatments.

“This provides real breakthroughs in understanding the genetics of female fertility,” he said.

“This could be useful in developing new treatments for infertility in certain circumstances and new strategies for contraceptives as well.”

 

This post originally appeared on ABC News.

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