Genomics and Computational Biology Graduate Group, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Int J Epidemiol. 2020 Jun 1;49(3):1022-1031. doi: 10.1093/ije/dyaa050.
Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized.
To further elucidate these factors, we conducted a genetic correlation analysis using cross-trait linkage disequilibrium (LD) score regression between migraine headache and 47 traits from the UK Biobank. We then tested for possible causality between these phenotypes and migraine, using Mendelian randomization. In addition, we attempted replication of our findings in an independent genome-wide association study (GWAS) when available.
We report multiple phenotypes with genetic correlation (P < 1.06 × 10-3) with migraine, including heart disease, type 2 diabetes, lipid levels, blood pressure, autoimmune and psychiatric phenotypes. In particular, we find evidence that blood pressure directly contributes to migraine and explains a previously suggested causal relationship between calcium and migraine.
This is the largest genetic correlation analysis of migraine headache to date, both in terms of migraine GWAS sample size and the number of phenotypes tested. We find that migraine has a shared genetic basis with a large number of traits, indicating pervasive pleiotropy at migraine-associated loci.
全球近五分之一的人口患有偏头痛，但这种疾病的风险因素仍未得到充分描述。
为了进一步阐明这些因素，我们使用 UK Biobank 中偏头痛头痛和 47 种特征之间的跨特征连锁不平衡（LD）分数回归进行了遗传相关性分析。然后，我们使用孟德尔随机化测试了这些表型与偏头痛之间可能存在的因果关系。此外，当可用时，我们尝试在独立的全基因组关联研究（GWAS）中复制我们的发现。
我们报告了与偏头痛具有遗传相关性的多种表型（P < 1.06 × 10-3），包括心脏病、2 型糖尿病、血脂水平、血压、自身免疫和精神表型。特别是，我们发现证据表明血压直接导致偏头痛，并解释了钙与偏头痛之间先前提出的因果关系。
这是迄今为止偏头痛头痛的最大遗传相关性分析，无论是偏头痛 GWAS 样本量还是测试的表型数量都是如此。我们发现偏头痛与许多特征具有共同的遗传基础，这表明偏头痛相关基因座存在普遍的多效性。
