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USC twin study shows how geography and genes increase multiple sclerosis risk

A new study of twins in the Annals of Neurology online suggests that living far north of the equator significantly increases the risk of developing multiple sclerosis (MS) in those with genetic susceptibility to the disease.

By following more than 700 pairs of twins diagnosed with MS, researchers from the Keck School of Medicine found that although northern latitudes account for only 24 percent of the population, they contributed a higher proportion (44 percent) of all twin cases of MS.

Locations categorized as “northern” included Canada or states at or above 42 degrees north latitude, including Alaska, Oregon, Washington, Idaho, Montana, Nebraska, North Dakota, South Dakota, Wyoming, Michigan, Minnesota, Wisconsin, Connecticut, Maine, Massachusetts, New Hampshire, New York, Rhode Island and Vermont.

Twins were divided into two categories, either monozygotic (identical genetic makeup, coming from one egg) or dizygotic (fraternal twins, coming from two separate eggs).

An effect seen more commonly in monozygotic twins suggests a heavier role for genetics.

The concordance (both twins being diagnosed with MS) among identical twin pairs born in the north was nearly twice as high as among those born elsewhere (18.6 percent vs. 9.5 percent). There was significantly less concordance among fraternal twins.

“We’ve known that MS is more common the farther away from the equator you get,” said Thomas Mack, professor of preventive medicine at the Keck School and lead author of the study.

“By looking at the number of times this occurs in twins—both identical and fraternal twins—we could see whether it was just a matter of latitude or if there is something else. This study suggests there’s more concordance among identical twins, which means there is some environmental exposure and it is interacting with the genes,” he said.

If environment alone were responsible for the increased incidence of both members of the twin pair getting MS, there would be similarly high concordance among fraternal twins, he noted. The study did not suggest that, however, showing instead that both identical twins were far more likely to get the disease than both fraternal twins.

In fact, despite clear evidence of a much higher incidence of MS among women, the study found high concordance in both male and female identical twins, implying “that mechanisms of inheritance are probably identical by sex. In other words, genetic susceptibility trumps the traditional bias against MS in most males.

Northern residence also contributed significantly to earlier onset of the disease. The researchers suggest that an early onset in the north could represent an early environmental deficit in protection, such as less opportunity for early exposure to the sun, or for unknown reasons to an unrecognized causal factor, such as a virus. “It may even be that exposure to the sun interrupts whatever effect a virus has,” said Mack.

Talat Islam, W. James Gauderman, Wendy Cozen, Ann S. Hamilton, Margaret E. Burnett and Thomas M. Mack, “Differential Twin Concordance for Multiple Sclerosis by Latitude of Birthplace.” The study was supported by the Multiple Sclerosis Society, the NIH (National Institute of Neurological Disease and Stroke) and the National Cancer Institute.

USC twin study shows how geography and genes increase multiple sclerosis risk

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