Chasman Daniel I, Schürks Markus, Kurth Tobias
Division of Preventive Medicine, Brigham and Women's Hospital, USA Harvard Medical School, USA
Department of Neurology, University Hospital Essen, Germany.
Cephalalgia. 2016 Jun;36(7):692-703. doi: 10.1177/0333102416638519. Epub 2016 Mar 24.
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.
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.
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.
虽然偏头痛的最准确诊断通常需要依据严格诊断标准进行临床问诊，但在基于人群的研究中通过问卷确定偏头痛的另一种方法，在发现影响偏头痛风险的常见基因变异方面发挥了重要作用。这一结果可能令人惊讶。基于人群的方法常因区分偏头痛与其他原发性头痛形式的能力有限而受到批评。因此，重新审视关于基于人群确定偏头痛的主流观点，以评估这种方法在深入了解偏头痛遗传学及病理生理学方面的潜在价值很有必要。
我们回顾了近期的研究结果，这些结果表明基于人群的方法之所以成功，是因为即使存在引入表型和基因异质性的风险，也有可能收集到比基于临床研究更大的样本。这些发现也与对许多其他常见复杂临床特征的遗传基础的新认识相一致。然而，在研究偏头痛遗传学的某些特定方面时，基于临床的确定方法及其他研究环境仍将比基于人群的方法更有效。
我们认为，偏头痛的详细遗传结构、方法学的各个方面以及基于人群确定所达到的最终样本量，将是这种偏头痛及其合并症基因分析方法未来成功的关键决定因素。
