May 3, 2018 - Science

New clues about how migraines are inherited

DNA sequence

DNA sequence. Photo: Getty Images

Common genetic variations may play a greater role in the onset, severity and heredity of migraines than previously thought, according to new research published today in the journal Neuron.

Why it matters: The cause of migraines remain elusive, but genetics is believed to play a role as 90% of people who affected by them have a family history of migraines. One in four U.S. households has someone with the disorder, which affects about 39 million Americans — about 90% of them are unable to work or function normally when they have one.

Background: About one-third of people who get migraines can predict the onset of one because they first get visual disturbances called an "aura," often flashing lights, zig-zag lines or a temporary loss of vision. The Mayo Clinic lists some of the triggers and risks.

Details of the study: Researchers looked at three genetic mutations (CACNA1A, ATPIA2, and SCN1A), which have been found to be causative in severe migraines and thought to play a role in most others as well.

  • In the study, which involved 1,589 families with 8,319 individuals, researchers compare the impact from the three genes to a group of common risk genes that could collectively influence how and when a migraine occurs. They compared this against a population cohort of 14,470 people.
  • Study author Aarno Palotie tells Axios they were "surprised" to find the common variants played a greater role in migraines than the three genetic mutations. They also found that, on average, the greater the number of common variants, the more severe the symptoms and the earlier the age of the onset of the disease.
"[O]ur decades of thinking that penetrant mutations would be important contributors for the phenotype in migraine families, might not be right."
— Palotie, from the Institute for Molecular Medicine in Finland and the Broad Institute of MIT and Harvard University

Possible origins: Meanwhile, another study published today in PLOS Genetics suggests our ancestors developed a migraine-causing gene variant as they migrated north to help them adapt to the colder climate. The team examined the gene TRPM8, which is the only known receptor in humans that mediates the sensation to moderate cold — and is also believed to play a role in migraines.

  • They looked at genetic data from more than 1,200 modern humans in various parts of the world as well as from ancient people who lived between 3,000 and 8,500 years ago.
  • 5% of people with Nigerian ancestry carry the TRPM8 variant whereas 88% of the people with Finnish ancestry possess that variant.
"This study is a step towards better understanding how humans may have biologically adapted to the different climates that we inhabit. Further, it shows that risk alleles for disease may be at high frequency simply as a side effect of past evolutionary processes (in this case, adaptation)."
— Study author Aida Andres, UCL Genetics Institute and Max Planck Institute for Evolutionary Anthropology

Recent treatment research:

The New England Journal of Medicine says the next frontier of migraine medicines may target a protein called CGRP that is believed to transmit migraine pain signals. NPR reports 2 new drugs targeting CGRP are being considered by the Food and Drug Administration over the next couple months.

Go deeper: STAT goes into the study on common genetic variants in families and New Scientist writes about how adaptation to the cold may be a cause of migraines.

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