The study is published on May 3 in the
‘A group of genes, as opposed to specific genes could be more responsible in causing the risk of migraines that tend to run in certain families.’
Scientists have known that migraines
tend to run in families but have
not been able to explain exactly how.
"For a long time, we have been
wondering why a common disease (like migraines) aggregates in families,"
said Aarno Palotie of the Institute for Molecular Medicine in Finland and the
Broad Institute of MIT and Harvard in Cambridge, Mass.
Basis of Migraines
Earlier research on migraines has
identified that migraines might run in families in two ways. Performing linkage
studies, scientists have identified
three genes (CACNA1A, ATP1A2 and SCN1A) that are associated with hemiplegic
, which is a severe form of the condition that could cause
stroke-like symptoms. These genes follow
the Mendelian inheritance model,
which means that the child must inherit
the dominant allele
(a form of gene) from one parent in order to get
hemiplegic migraine (in other words a trait). If they get the two recessive alleles
from the parents, they will not experience migraine.
The other way scientists have found by
which migraines could run in families involves polygenic inheritance. When a person inherits a polygenic trait,
it means a group of genes worked together to produce that characteristic
Each common genetic variant or allele
might only have a small effect
individually but put together the common variants tend to influence the trait
or disease risk in this case the child gets.
- What kind of Genetics Influences Migraines
Palotie and his colleagues performed
some studies to answer questions about how migraines are inherited in families;
that is, whether it was due to the few, powerful Mendelian genes or due to the
polygenic accumulation of common variants, or was it a combination of both.
The researchers first developed a polygenic risk score to
determine how much disease risk was caused by the common variants
gathered data from a genome-wide association study, which is a type of study
that compares genomes of individuals and finds the locations on chromosomes
(known as gene loci) that differ in people with a disease. There were possibly
thousands of loci linked to migraines that were incorporated into the polygenic
Next, the researchers wanted to test
how much of an influence the polygenic
risk score and the three known Mendelian migraine-linked genes played within a
large family study of migraine sufferers in Finland
. The study involved
1,589 families (made up of 8,319 individuals) of known migraine sufferers;
their medical history and genetic data were collected. The family migraine
cohort was the test group and it was compared to a large control group that had
14,470 people total, including 1,101 people with migraine.
of the StudyThe
researchers discovered that the polygenic common variants were driving migraine
risk more than the three Mendelian genes.
The data showed that common
polygenic variants had a greater influence in determining things like, if a
person's migraines started at an earlier age, if a person experienced more
severe migraines, or if migraines ran in a person's family.
The researchers also identified 45
families among the 1,589 families that suffered from a hemiplegic migraine and
sequenced their genes. More cases of migraines were driven by common variants
while the rare Mendelian genes only influenced migraines in four out of 45
families. Hence, the study proved that the
three rare but powerful Mendelian genes linked to a migraine influenced
migraine risk to a much lesser extent than what the researchers expected.
"This really shows, in a very big
sample set, that common variants are very important factors in aggregation of
migraines in the family," said Palotie.
"This is of special interest for
drug development," said Palotie. Even if Mendelian variants don't drive
the majority of migraine cases, scientists can research how these genes impact
biological pathways responsible for migraine symptoms and potentially develop
drugs to target those pathways.
Future studies would involve more
genome sequencing and larger studies to find both more common variants linked
to migraines and more Mendelian variants.
A headache that is throbbing or
pulsing usually only on one side of the head is a migraine. During a migraine attack
people are sensitive to
light and sound and may become nauseous and vomit.
Fifteen to twenty percent of adults
in developed countries suffer from migraines and women experience migraines more than men
triggers could be anxiety, stress
imbalance in food or sleep, and
hormonal changes (in women).
Migraines are now believed to be
controlled by genes that control the activity of some brain cells. Medicines
can help relieve the symptoms or prevent an attack from occurring.
- Padhraig Gormley, Mitja I. Kurki, Marjo Eveliina Hiekkala, Kumar Veerapen.et.al . Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families, Neuron (2018).DOI: https://doi.org/10.1016/j.neuron.2018.04.014
- Migraine - (https://medlineplus.gov/migraine.html)
- What are genome-wide association studies? - (https://ghr.nlm.nih.gov/primer/genomicresearch/gwastudies)