Dataset Information

A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N=223,773).

ABSTRACT: BACKGROUND:Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort. METHODS:We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls. RESULTS:We identified 3343 SNPs which reached the genome-wide significance level of P<5×10-8. The SNPs were located in 28 loci, with the top SNP of rs11172113 in the LRP1 gene having a P value of 4.92×10-47. Of the 28 loci, 14 have previously been associated with migraine. Among 14 new loci, rs77804065 with a P value of 5.87×10-15 in the LINC02210-CRHR1 gene was the top SNP. Significant relationships between multiple brain tissues and genetic associations were identified through tissue expression analysis. We also identified significant positive genetic correlations between headache and many psychological traits. CONCLUSIONS:Our results suggest that brain function is closely related to broadly-defined headache. In addition, we found that many psychological traits have genetic correlations with headache.

SUBMITTER: Meng W

PROVIDER: S-EPMC5898025 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N=223,773).

Meng Weihua W Adams Mark J MJ Hebert Harry L HL Deary Ian J IJ McIntosh Andrew M AM Smith Blair H BH

EBioMedicine 20180131

<h4>Background</h4>Headache is the most common neurological symptom and a leading cause of years lived with disability. We sought to identify the genetic variants associated with a broadly-defined headache phenotype in 223,773 subjects from the UK Biobank cohort.<h4>Methods</h4>We defined headache based on a specific question answered by the UK Biobank participants. We performed a genome-wide association study of headache as a single entity, using 74,461 cases and 149,312 controls.<h4>Results</h ...[more]

PMID: 29397368

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Project description:Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.

Dataset Information

A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N=223,773).

Publications

A Genome-Wide Association Study Finds Genetic Associations with Broadly-Defined Headache in UK Biobank (N=223,773).

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