Migraine heritability and beyond: A scoping review of twin studies

OBJECTIVE: This scoping review aimed to summarize current knowledge from twin studies on migraine. Migraine heritability, genetic correlations with migraine comorbid disorders, and the use of discordant twin pairs in migraine research are described. Further, the review considers the unused potential of twin studies in migraine research and reflects on future directions.

BACKGROUND: Twin studies can be used to understand how heritable and environmental factors influence human traits and disorders. The classical twin design compares the resemblance of a trait in monozygotic twins to that in dizygotic twins. The classical twin design can be extended to estimate the genetic correlation between disorders, model causality, and describe differences within discordant twin pairs.

METHODS: Studies focusing on migraine and using a twin study design were included. The search was performed on the PubMed-MEDLINE database using the search terms "migraine" AND "twin" OR "twins." It was done in May 2023, rerun in November 2023, and managed with the Covidence software.

RESULTS: The search identified 52 twin studies on migraine. In 24 papers, the heritability of migraine was estimated with a classical twin design. Heritability estimates ranged from 0.36 to 0.48 for studies with adults, both men and women, and unspecified migraine. Migraine heritability was predominantly estimated with twin cohorts of North European ancestry, and only two studies examined migraine subtypes. A multilevel classical twin design was used in 11 studies to examine the co-occurrence between migraine and comorbid disorders. The differences within migraine discordant twin pairs were examined in nine studies.

CONCLUSION: The heritability of migraine was estimated with a classical twin design in twin cohorts from seven different countries, with remarkably similar results across studies. Future studies should include migraine subtypes and twin cohorts of non-North European ancestry to better reflect the global population. Beyond heritability estimations, the twin method is a valuable tool for understanding causality and describing differences within discordant twin pairs. Despite more than 80 years of twin studies in migraine research, the twin design has a large unused potential to advance our understanding of migraine.