Finnish researchers have always played a major role in elucidating the genetics of migraine. This is, of course, helped by the fact that Finns are very research-oriented. Here, I highlight a study led by Professor Aarno Palotie. The study is titled Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families (reference below). A quick glance at the study immediately reveals that genetic research is a statistical analysis of large numbers.
The article investigates the genetic background of migraine heritability by analyzing 1,589 Finnish families and comparing their genetic profile to control subjects from a corresponding population group and to random cases.
Polygenic Risk Scores and Familial Aggregation
Familial migraine is significantly explained by polygenic risk scoring (PRS), which reflects the combined effect of many common genetic variants, each of which slightly increases the risk. In familial migraine, the PRS burden was significantly higher (1.76) than in population-based cases (1.32). The study shows that polygenic burden is a significant cause of heritable disease in families.
Genetic Burden of Migraine Subtypes
An elevated polygenic burden was observed in all familial migraine subtypes, including migraine without aura, migraine with typical aura, and hemiplegic migraine. The disease burden was highest for hemiplegic migraine (1.96). Significant differences in PRS levels were observed between migraine subtypes: typical aura and hemiplegic migraine were higher than migraine without aura. Typical aura (= a zigzag pattern moving in the visual field) without headache showed a very low polygenic burden, which did not differ from the control group.
Rare and Common Genetic Variants
Only a small proportion, about 10%, of familial hemiplegic migraine cases were associated with previously known monogenic diseases, particularly common in Central Europe. The majority of Finns had a high polygenic risk level, which highlights the importance of numerous genetic changes instead of rare, strong genetic defects.
Age of Onset and Severity of Symptoms
Genetic burden is higher when migraine starts early and, to a lesser extent, when clinical symptoms are more severe. Migraine patients who used triptan medication, meaning they needed more effective medication, had a higher-than-average PRS.
Risk of Migraine Inheritance
According to the study, migraine-related genetic variations were passed from parents to symptomatic children more than statistically expected, which confirms the importance of variation caused by several different genes.
Conclusions
Both common and rare forms of migraine, including hemiplegic migraine, appear to be influenced by polygenic burden. The genetic background of familial migraine is not primarily caused by changes in single genes, but polygenic risk burden plays a very important role in the onset of migraine in families.
Reference: Cell – Common Variant Burden Contributes to the Familial Aggregation of Migraine in 1,589 Families
Markku Nissilä, neurologist
Frequently asked questions about migraine inheritance
Can migraine be inherited?
Yes. According to research, the genetic risk of migraine is passed from parents to children through several genetic mutations.
Is there a "migraine gene"?
Not a single one. Migraine arises from the combined effect of many small genetic changes.
Can a genetic test predict migraine risk?
Currently, a single genetic test cannot reliably predict the risk, as it is a polygenic phenomenon.
If parents have migraine, will the child definitely get it?
Not necessarily. Genes increase susceptibility, but environment and lifestyle also play a big role.
How does knowledge of heredity help?
By understanding the genetic background, we can identify risk factors earlier and seek appropriate treatments in time.
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