Next came candidate gene association studies. “We were involved in the 5-HT transporter gene studies,” Dr. Olesen said. “Every now and then, people have found that there is an association with a particular candidate gene. But when other people have done the same thing, they have been unable to confirm it. So at the moment I’m not sure that we really are much better off after all these association studies focusing on candidate genes. Nothing much has been found that is solid.” About that time, around 10 to 15 years ago, sib pair analysis was popular in genetic research. “We tried to collect all the patients that we could from Danish registries, and then we looked particularly for sib pairs,” Dr. Olesen said. “We got a lot of them, and we got a lot of additional cases. So we ended up with almost 1,000 patients with migraine with typical aura. But sib pair analysis didn’t yield anything in the genetic analysis, and the same thing has happened with other people who tried to use sib pairs. To my knowledge, nobody else has found anything based on sib pair analysis.”
The Future of Migraine Genetics
Major advances have been made in the genetics of familial hemiplegic migraine, but the same cannot be said for the genetics of the common types of migraine. But, as Dr. Olesen pointed out, the three known genes for familial hemiplegic migraine only explain about half of the cases of that disorder, “so if somebody finds more genes in familial hemiplegic migraine in the smaller families, then those, in theory, could be involved in the common types of migraine.” In this era of genetic research, that would involve going to the affected families, both large and small, and investigating with whole genome sequencing. This type of research, Dr. Olesen speculated, may reveal not only rare but high-risk genes, but also common but low-risk genes.
—Glenn S. Williams