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Correspondence to Dr Hakon Hakonarson, Center for Applied Genomics, Children’s Hospital of Philadelphia, Leonard Madlyn Abramson Research Center, Philadelphia, PA 19104-4318, USA; [email protected]
Introduction
Migraine is a common neurological disorder characterised by recurrent and intense headaches.1 Although the mechanism of migraine is still unknown, migraines are believed to be caused by the interactions of multiple environmental and genetic factors.1 Twin studies have revealed heritability estimates of migraine ranging from 34% to 51%.2 Consistent with the high heritability estimates, genome-wide association studies (GWASs) of European adults have successfully identified many migraine susceptibility genes involved in neuronal and vascular mechanism.3 4 As the origins of migraine can be traced into childhood and adolescence for many adult sufferers, the early onset of migraine may reflect elevated biological predisposition or increased susceptibility to environmental risk factors. In addition, as the prevalence of migraines varies across ethnicities, the genetic risk factors may be different in African ancestries and European ancestries. To our knowledge, no large-scale GWAS has been performed in either children or African Americans with migraine.
Methods
Sample collection
Case subjects were defined as subjects with a diagnosis of migraine (ICD9 (International Classification of Diseases, ninth revision) code: 346.00–346.93) and registered through the electronic medical record (EMR) of the Children’s Hospital of Philadelphia (CHOP). All patients fulfilled the International Headache Society diagnostic criteria (ICHD-3b)5 for migraine. The number of patients diagnosed with migraine with and without aura was provided in online supplementary table S1.
Supplementary file 1
All blood samples were collected at the time of diagnosis, and most were annotated with clinical information comprising gender and age at diagnosis. Control subjects were recruited from the Philadelphia region through the CHOP Healthcare Network, including four primary care clinics and several group practices and outpatient practices that included well-child visits. Eligibility criteria for control subjects were (1) self-reporting as Caucasian or African American, (2) availability of 1.5 µg of high-quality DNA from peripheral blood mononuclear cells and (3) no serious underlying medical disorder, including mental disorders (ICD9 code: 290.0–319). The Research Ethics Board of CHOP provided written informed consent from all subjects by nursing and medical assistant staff under the direction of CHOP clinicians. SNP genotyping was performed using the Illumina Infinium II...