Dataset Information

Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache.

ABSTRACT:

Background

Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: Siewert KM

PROVIDER: S-EPMC7394956 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Publications

Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache.

Siewert Katherine M KM Klarin Derek D Damrauer Scott M SM Chang Kyong-Mi KM Tsao Philip S PS Assimes Themistocles L TL Davey Smith George G Voight Benjamin F BF

International journal of epidemiology 20200601 3

<h4>Background</h4>Nearly a fifth of the world's population suffer from migraine headache, yet risk factors for this disease are poorly characterized.<h4>Methods</h4>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 attemp ...[more]

PMID: 32306029

Similar Datasets

Project description:IntroductionIt is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related.AimUsing a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO.MethodsGene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO.ResultsWe found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10(-4)). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue.ConclusionsOur results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

Dataset Information

Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache.

Background

Methods

Results

Conclusions

Publications

Cross-trait analyses with migraine reveal widespread pleiotropy and suggest a vascular component to migraine headache.

Similar Datasets

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