A genome-wide association study finds novel genetic associations with broadly-defined headache in UK Biobank (N = 223,773)

AbstractHeadache 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. 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. We identified 3,343 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.Positive relationships (P < 0.001) between multiple brain tissues and genetic associations were identified through tissue expression analysis, whereas no vascular related tissues showed significant relationships. We identified several significant positive genetic correlations between headache and other psychological traits including neuroticism, depressive symptoms, insomnia, and major depressive disorder.Our results suggest that brain function is closely related to broadly-defined headache. In addition, we also found that many psychological traits have genetic correlations with headache.

Download Full-text

P15 Cervical intraepithelial neoplasia and cervical cancer: a genome wide association study (GWAS) of the UK biobank cohort

10.1136/ijgc-2019-esgo.78 ◽

2019 ◽

Author(s):

S Bowden ◽

I Kalliala ◽

M Wielscher ◽

B Bodinier ◽

J Flanagan ◽

...

Keyword(s):

Cervical Cancer ◽

Association Study ◽

Cervical Intraepithelial Neoplasia ◽

Genome Wide Association Study ◽

Intraepithelial Neoplasia ◽

Genome Wide Association ◽

Uk Biobank ◽

Genome Wide ◽

A Genome ◽

The Uk

Download Full-text

A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank

Human Molecular Genetics ◽

10.1093/hmg/ddaa058 ◽

2020 ◽

Vol 29 (8) ◽

pp. 1396-1404 ◽

Cited By ~ 2

Author(s):

Weihua Meng ◽

Brian W Chan ◽

Cameron Harris ◽

Maxim B Freidin ◽

Harry L Hebert ◽

...

Keyword(s):

Association Study ◽

Shoulder Pain ◽

Genetic Variants ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Uk Biobank ◽

Genome Wide ◽

A Genome ◽

Significant Locus ◽

The Uk

Abstract Background Common types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203 309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK. Methods A genome-wide association study was performed adjusting for age, sex, BMI and nine population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication. Results We identified three genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 × 10−11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 × 10−10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 × 10−8 for rs62053992. In the replication stage, among four significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). Conclusions We have identified three loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain.

Download Full-text

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

EBioMedicine ◽

10.1016/j.ebiom.2018.01.023 ◽

2018 ◽

Vol 28 ◽

pp. 180-186 ◽

Cited By ~ 21

Author(s):

Weihua Meng ◽

Mark J. Adams ◽

Harry L. Hebert ◽

Ian J. Deary ◽

Andrew M. McIntosh ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Uk Biobank ◽

Genetic Associations ◽

Genome Wide ◽

A Genome

Download Full-text

A genome-wide association study finds genetic variants associated with neck or shoulder pain in UK Biobank

10.1101/2020.01.20.913228 ◽

2020 ◽

Author(s):

Weihua Meng ◽

Brian W Chan ◽

Cameron Harris ◽

Maxim B Freidin ◽

Harry L Hebert ◽

...

Keyword(s):

Association Study ◽

Shoulder Pain ◽

Genetic Variants ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Chromosome 17 ◽

Uk Biobank ◽

Genome Wide ◽

A Genome ◽

The Uk

ABSTRACTBackgroundCommon types of musculoskeletal conditions include pain in the neck and shoulder areas. This study seeks to identify the genetic variants associated with neck or shoulder pain based on a genome-wide association approach using 203,309 subjects from the UK Biobank cohort and look for replication evidence from the Generation Scotland: Scottish Family Health Study (GS:SFHS) and TwinsUK.MethodsCases in the UK Biobank were determined by a question which asked the participants if they had experienced pain in the neck or shoulder in the previous month influencing daily activities. Controls were the UK Biobank participants who reported no pain anywhere in the last month. A genome-wide association study was performed adjusting for age, sex, BMI and 9 population principal components. Significant and independent genetic variants were then sent to GS:SFHS and TwinsUK for replication.ResultsWe identified 3 genetic loci that were associated with neck or shoulder pain in the UK Biobank samples. The most significant locus was in an intergenic region in chromosome 17, rs12453010, having P = 1.66 × 10-11. The second most significant locus was located in the FOXP2 gene in chromosome 7 with P = 2.38 × 10-10 for rs34291892. The third locus was located in the LINC01572 gene in chromosome 16 with P = 4.50 × 10-8 for rs62053992. In the replication stage, among 4 significant and independent genetic variants, rs2049604 in the FOXP2 gene and rs62053992 in the LINC01572 gene were weakly replicated in GS:SFHS (P = 0.0240 and P = 0.0202, respectively). None of the single nucleotide polymorphisms (SNPs) were replicated in the TwinsUK cohort (P > 0.05).ConclusionsWe have identified 3 loci associated with neck or shoulder pain in the UK Biobank cohort, two of which were weakly supported in a replication cohort. Further evidence is needed to confirm their roles in neck or shoulder pain.SignificanceThis is the first genome-wide association study on neck or shoulder pain. We have identified 3 genetic loci (an intergenic region in chromosome 17, the FOXP2 gene in chromosome 7, and the LINC01572 gene in chromosome 16) that are associated with neck or shoulder pain using the UK Biobank cohort, among which the FOXP2 gene and the LINC01572 gene were weakly replicated by the Generation Scotland: Scottish Family Health Study (P < 0.05). The SNP heritability was 0.11, indicating neck or shoulder pain is a heritable trait. The tissue expression analysis suggested that neck or shoulder pain was related to multiple brain tissues, indicating the involvement of neuron function. The results will inform further research in the characterisation of the mechanisms of neck or shoulder pain.

Download Full-text

Genome-wide association study of vegetarianism in UK Biobank identifies association with VRK2

Wellcome Open Research ◽

10.12688/wellcomeopenres.16396.1 ◽

2020 ◽

Vol 5 ◽

pp. 291

Author(s):

Georgina K. Fensom ◽

Karl Smith-Byrne ◽

Colm D. Andrews ◽

Tim J. Key ◽

Ruth C. Travis

Keyword(s):

Association Study ◽

Fluid Intelligence ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Genome Wide Association ◽

Future Research ◽

Age At Menarche ◽

Uk Biobank ◽

Genome Wide ◽

A Genome

Prospective studies have observed differences in risks for several health outcomes when comparing meat-eaters and vegetarians, but the mechanisms underlying these differences remain uncertain. Identifying genetic factors related to vegetarianism may be valuable for assessing causality. We report a genome-wide association study (GWAS) of vegetarianism in 367,198 participants from UK Biobank. We identified one locus, rs10189138, near the vaccinia related kinase 2 (VRK2) gene, significantly associated with vegetarianism (β=0.153, p=3x10-8). The associations between rs10189138 and 40 traits were calculated, and the rs10189138 T allele (MAF=0.12) was found to be significantly associated with greater height, after controlling the false discovery rate (FDR). Correlations between genetically predicted vegetarianism and 855 other genetically predicted traits were also calculated, and vegetarianism had significant positive genetic correlations with fluid intelligence and age at menarche, after controlling the FDR. Future research on an independent sample is needed to see if this GWAS result can be replicated.

Download Full-text

Genome-Wide Association Meta-Analysis Supports Genes Involved in Valve and Cardiac Development to Associate With Mitral Valve Prolapse

Circulation Genomic and Precision Medicine ◽

10.1161/circgen.120.003148 ◽

2021 ◽

Author(s):

Mengyao Yu ◽

Sergiy Kyryachenko ◽

Stephanie Debette ◽

Philippe Amouyel ◽

Jean-Jacques Schott ◽

...

Keyword(s):

Mitral Valve ◽

Association Study ◽

Genome Wide Association Study ◽

Cardiac Development ◽

Meta Analysis ◽

Genome Wide Association ◽

Uk Biobank ◽

Additional Risk ◽

Genome Wide ◽

The Uk

Background: Mitral valve prolapse (MVP) is a common cardiac valve disease, which affects 1 in 40 in the general population. Previous genome-wide association study have identified 6 risk loci for MVP. But these loci explained only partially the genetic risk for MVP. We aim to identify additional risk loci for MVP by adding data set from the UK Biobank. Methods: We reanalyzed 1007/479 cases from the MVP-France study, 1469/862 controls from the MVP-Nantes study for reimputation genotypes using HRC and TOPMed panels. We also incorporated 434 MVP cases and 4527 controls from the UK Biobank for discovery analyses. Genetic association was conducted using SNPTEST and meta-analyses using METAL. We used FUMA for post-genome-wide association study annotations and MAGMA for gene-based and gene-set analyses. Results: We found TOPMed imputation to perform better in terms of accuracy in the lower ranges of minor allele frequency below 0.1. Our updated meta-analysis included UK Biobank study for ≈8 million common single-nucleotide polymorphisms (minor allele frequency >0.01) and replicated the association on Chr2 as the top association signal near TNS1 . We identified an additional risk locus on Chr1 ( SYT2 ) and 2 suggestive risk loci on chr8 ( MSRA ) and chr19 ( FBXO46 ), all driven by common variants. Gene-based association using MAGMA revealed 6 risk genes for MVP with pronounced expression levels in cardiovascular tissues, especially the heart and globally part of enriched GO terms related to cardiac development. Conclusions: We report an updated meta-analysis genome-wide association study for MVP using dense imputation coverage and an improved case-control sample. We describe several loci and genes with MVP spanning biological mechanisms highly relevant to MVP, especially during valve and heart development.

Download Full-text

Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112,117)

10.1101/116707 ◽

2017 ◽

Cited By ~ 8

Author(s):

Toni-Kim Clarke ◽

Mark J. Adams ◽

Gail Davies ◽

David M. Howard ◽

Lynsey S. Hall ◽

...

Keyword(s):

Alcohol Consumption ◽

Association Study ◽

Genome Wide Association Study ◽

Hdl Cholesterol ◽

Genome Wide Association ◽

P Value ◽

Uk Biobank ◽

Genome Wide ◽

A Genome ◽

Genetic Overlap

AbstractAlcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well known genetic variants in alcohol metabolizing genes, e.g. ALDH2, ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112,117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 8 independent loci. These include SNPs in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and 2 loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, PXDN, CADM2 and TNFRSF11A. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (CRHR1, DRD2), and genes previously associated with alcohol consumption (AUTS2). GCTA-GREML analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (S.E.=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation between male and female alcohol consumption was 0.73 (S.E.=0.09, p-value = 1.37 x 10−16). Using LD score regression, genetic overlap was found between alcohol consumption and schizophrenia (rG=0.13, S.E=0.04), HDL cholesterol (rG=0.21, S.E=0.05), smoking (rG=0.49, S.E=0.06) and various anthropometric traits (e.g. Overweight, rG=-0.19, S.E.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies 4 novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

Download Full-text