FINAL REPORT: Towards a Migraine Genetics Population Laboratory: Building on the American Migraine Prevalence and Prevention (AMPP) Study

Summary

Migraine is a major public health concern that has an impact on individual sufferers, their families, the healthcare system, employers and society. It is a complex disorder influenced by numerous genetic and environmental risk factors. Although a number of genes have been identified as being involved in migraine and pain progression, there are likely many unknown genetic factors at play. Our ultimate goal is to establish a Migraine Genetics Population Laboratory (MGPL) at the Albert Einstein College of Medicine to study the genetics of migraine. The goal of the current study was to examine the feasibility of collecting usable genetic data from a large population sample through the mail.

We sent genetic sample collection kits to participants from the American Migraine Prevalence and Prevention (AMPP) study, the largest and longest population study of persons with migraine in the world to date. DNA collection kits and consent form packets were mailed to 240 AMPP questionnaire respondents: 80 individuals in each of three headache status groups: No headache (control group), episodic migraine, and chronic migraine. Each subgroup was equally divided into two groups by the presence of clinical depression. A total of 152 samples were returned (63%), yielding 147 samples with usable DNA (61%).

Return rates were higher among persons with episodic migraine (68%) and chronic migraine (69%) compared to those in the no headache control group (54%), indicating, as would be expected, that response rates were higher among those with migraine. These data will be used as pilot feasibility data in support of an NIH grant to study the genetics of migraine on a large-scale basis. In addition, this sample may be used to pilot test the viability of these samples in genotyping using a dedicated gene array chip, the Pain Research Panel, which assays variants characterizing over 350 genes known to be involved in biological pathways relevant to nociception, inflammation, and mood.

Based on the results of this study, we demonstrated that it is possible to collect DNA samples from both subjects with migraine and without headache through the mail using a genetic testing saliva kit. Furthermore, the returned samples produced good quality, usable DNA that could be used in various genetic studies that will help us better understand the underlying causes and potential treatments of migraine.

Hypothesis v. Findings

Our aim was to demonstrate the feasibility of and to optimize procedures for the collection of DNA by saliva in the AMPP, in individuals with episodic migraine, chronic migraine, and non-migraine control subjects.

Hypothesis 1: Among selected AMPP participants we can achieve 90% participation in saliva. We will explore the role of recruiting and reminder phone calls and repeated mailings to optimize participation rates and minimize cost.

Result: We received a 63% return response rate. We reviewed many possible combinations of incentive amounts and numbers of follow-ups (phone calls, postcards) as well as the sequencing and timing of the mailing (e.g. to mail the consent form and kit together vs. mailing the consent form first, waiting for consent to participate then mailing the genetic data collection kit).

Hypothesis 2: Among those who provide saliva, we will achieve a 90% yield of usable DNA. If DNA is un-usable, at least 80% of subjects will send a second usable sample when they are recontacted.

Result: Of those who provided DNA, 96.7% was usable. We did not have the funds to recontact, send new kits, and reanalyze data from the 5 subjects who provided data that was not usable. These results show that collecting genetic data through saliva through the mail is a viable collection method. The kits were effective and the samples are stable at room temperature for 18 months.

Hypothesis 3: Participation rates and yields will be similar across the 3 groups and will not differ by headache or demographic characteristics, minimizing the prospects for selection bias.

Result: We had an overall return rate of 63%. Return rates were higher among persons with episodic migraine (68%) and chronic migraine (69%) compared to those in the no headache control group (54%), indicating as would be expected that response rates were higher among those with migraine. Also, we can hypothesize that we have a strong relationship with the persons in the migraine group as we have followed them every year between 2004-2009, while we have been in contact with the non-headache control group in the years 2004, 2008 and 2009. We also found differences in the rate of return within groups by depression status and found that for the control group 48% of those without depression and 60 % of those with depression responded, and within the chronic migraine condition, 73% of those without depression and 65% of those with depression responded.  These results do not predict a particular hypothesis as they are in the opposite direction in the two groups. The rates of response within the episodic migraine sample were exactly the same by depression status.

Unanswered Questions

The primary question arising out of this research is how to achieve higher response rates. Possible approaches may lie in selection of participants, providing participants with clear rationale and answering questions about concerns they may have about giving genetic data, increasing compensation for participation, increasing follow-up via phone, mail, or in person, and the costs associated with each of these strategies. An in-person data collection paradigm may yield the highest participation rates, but the costs associated with this strategy may make it prohibitive.

What This Research Means To You

Our research demonstrates that collection by mail of usable genetic data from migraine sufferers is feasible and may yield answers to a myriad of questions regarding migraine heritability, expression, development, and progression.