title: Population-based approaches to genetics of migraine.
abstract: BACKGROUND
  While the most accurate diagnosis of migraine typically requires a clinical interview guided by strict diagnostic criteria, an alternative approach that ascertains migraine by questionnaire in population-based settings has been instrumental in the discovery of common genetic variants influencing migraine risk. This result may be surprising. Population-based approaches are often criticized for limited ability to distinguish migraine from other forms of primary headache. It is thus useful to revisit prevailing ideas about population-based ascertainment of migraine to evaluate the extent to which this approach has potential for additional insights into migraine genetics and therefore pathophysiology.
  
  
  BACKGROUND
  We review recent findings suggesting that the success of the population-based approach is derived from the possibility of collecting much larger samples than in the clinic-based setting even at the risk of introducing phenotypic and genetic heterogeneity. The findings are also consistent with new appreciations for the genetic basis of many other common, complex clinical characteristics. However, clinic-based ascertainment and other settings will remain more effective than population-based approaches for investigating certain, often very specific aspects of migraine genetics.
  
  
  CONCLUSIONS
  We argue that the detailed genetic architecture of migraine, various aspects of methodology, and the ultimate sample size achieved by population-based ascertainment will be critical determinants of the future success of this approach to genetic analysis of migraine and its comorbidities.
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, USA Harvard Medical School, USA dchasman@research.bwh.harvard.edu.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Chasman
authors.affiliation: Department of Neurology, University Hospital Essen, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schürks
authors.affiliation: Division of Preventive Medicine, Brigham and Women's Hospital, USA Institut of Public Health, Charité-Universitätsmedizin Berlin, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kurth
mesh_terms: D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008881:Migraine Disorders / Q000235:genetics*; D011159:Population Surveillance / Q000379:methods*
keywords: Migraine genetics; migraine heritability; migraine with aura; migraine without aura