Kossowsky Joe, Schuler Megan S, Giulianini Franco, Berde Charles B, Reis Ben, Ridker Paul M, Buring Julie E, Kurth Tobias, Chasman Daniel I
Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, United States.
Division of Clinical Psychology and Psychotherapy, University of Basel, Basel, Switzerland.
Front Neurol. 2021 Feb 12;11:617472. doi: 10.3389/fneur.2020.617472. eCollection 2020.
Migraine is heritable and formally diagnosed by structured criteria that require presence of some but not all possible migraine symptoms which include aura, several distinct manifestations of pain, nausea/vomiting, and sensitivity to light or sound. The most recent genome-wide genetic association study (GWAS) for migraine identified 38 loci. We investigated whether 46 single-nucleotide polymorphisms (SNPs), i.e., genetic variants, at these loci may have especially pronounced, i.e., selective, association with migraine presenting with individual symptoms compared to absence of migraine. Selective genetic associations of SNPs were evaluated through a likelihood framework in the Women's Genome Health Study (WGHS), a population-based cohort of middle-aged women including 3,003 experiencing migraine and 18,108 not experiencing migraine, all with genetic information. SNPs at 12 loci displayed significant selective association for migraine subclassified by specific symptoms, among which six selective associations are novel. Symptoms showing selective association include aura, nausea/vomiting, photophobia, and phonophobia. The selective associations were consistent whether the women met all formal criteria for diagnostic for migraine or lacked one of the diagnostic criteria, formally termed probable migraine. Subsequently, we performed latent class analysis of migraine diagnostic symptoms among 69,861 women experiencing migraine from the WGHS recruitment sample to assess whether there were clusters of specific symptoms that might also have a genetic basis. However, no globally robust latent migraine substructures of diagnostic symptoms were observed nor were there selective genetic associations with specific combinations of symptoms revealed among weakly supported latent classes. The findings extend previously reported selective genetic associations with migraine diagnostic symptoms while supporting models for shared genetic susceptibility across all qualifying migraine at many loci.
偏头痛具有遗传性，通过结构化标准进行正式诊断，这些标准要求存在部分而非全部可能的偏头痛症状，包括先兆、几种不同的疼痛表现、恶心/呕吐以及对光或声音敏感。最近一项针对偏头痛的全基因组遗传关联研究（GWAS）确定了38个基因座。我们调查了这些基因座上的46个单核苷酸多态性（SNP），即基因变异，与出现个体症状的偏头痛相比，是否与无偏头痛的情况有特别显著的关联，即选择性关联。通过女性基因组健康研究（WGHS）中的似然框架评估SNP的选择性遗传关联，该研究是一个基于人群的中年女性队列，包括3003名患偏头痛的女性和18108名未患偏头痛的女性，她们都有基因信息。12个基因座上的SNP对按特定症状分类的偏头痛显示出显著的选择性关联，其中6种选择性关联是新发现的。显示选择性关联的症状包括先兆、恶心/呕吐、畏光和畏声。无论这些女性是否符合偏头痛诊断的所有正式标准，还是缺少其中一项诊断标准（正式称为可能偏头痛），选择性关联都是一致的。随后，我们对WGHS招募样本中69861名患偏头痛的女性的偏头痛诊断症状进行了潜在类别分析，以评估是否存在可能也有遗传基础的特定症状群。然而，未观察到具有全球稳健性的偏头痛诊断症状潜在子结构，在支持力度较弱的潜在类别中也未发现与特定症状组合的选择性遗传关联。这些发现扩展了先前报道的与偏头痛诊断症状的选择性遗传关联，同时支持了许多基因座上所有符合条件的偏头痛共享遗传易感性的模型。
