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- Title
Lack of association between the MTHFR C677T variant and migraine with aura in an older population: Could selective survival play a role?
- Authors
Scher, Ann I; Eiriksdottir, Gudny; Garcia, Melissa; Feit, Preethy; Smith, Albert V; Harris, Tamara B; Roecklein, Kathryn A; Gudmundsson, Larus S; Gudnason, Vilmundur; Launer, Lenore J
- Abstract
Background: Several studies, but not all, of primarily middle-aged or younger adults have suggested that the commonMTHFR C677T variant is a genetic risk factor for migraine with aura (MA). Here, we consider whether this variant isassociated with MA risk in an older non-clinical population (AGES-Reykjavik cohort). Methods: Participants are a sub-sample (n=1976) of subjects from the Reykjavik Study (RS; mean age 50) and itscontinuation, AGES-RS (mean age 76).We estimated the relative odds of MA in TT versus CC carriers using multinomiallogistic regression. As both MA and the TT genotype may be linked with modestly reduced longevity, we performed asimple simulation to illustrate the effect that selective survival may have had on our observed gene-disease association.Results: TT versus CC carriers were at marginally reduced odds of MA (ORTTT 0.55 (0.3-1.0), p=0.07), significantly forwomen (ORTT 0.45 (0.2-0.9), p=0.03). Assuming the 'true' (e.g. mid-life) effect of the TT genotype is ORTT 1.26, from arecent meta-analysis, our simulation suggested that if 25-year mortality had been (hypothetically) 13% higher in MAsubjects with the TT versus CC genotype, the measured effect of the TT genotype on MA would have been attenuatedto non-significance (e.g. ORTT 1.00). Our observed protective effect was consistent with the most extreme selectivemortality scenario, in which essentially all of the previously reported increased mortality in MA subjects was (hypothetically)found in CT or TT carriers. Conclusion: The MTHFR 677TT genotype was associated with marginally reduced risk of MA in our older population. Oursimulation illustrated how even modest selective survival might obscure the apparent effect of a genetic or other riskfactor in older populations. We speculate that some of the heterogeneity previously observed for this particular geneticvariant may be due to age range differences in the studied populations.
- Subjects
METHYLENETETRAHYDROFOLATE reductase; GENETIC research; MIGRAINE; DISEASES in older people; DISEASE risk factors; GENETICS
- Publication
Cephalalgia, 2013, Vol 33, Issue 5, p308
- ISSN
0333-1024
- Publication type
Article
- DOI
10.1177/0333102412469739