Response to: ‘HLA-A* 31:01 is not associated with the development of methotrexate pneumonitis in the UK population: results from a genome wide association study’ by Bluett et al

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.

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135. GENOME-WIDE ASSOCIATION STUDY IDENTIFIES A LOCUS AT 7p15.2 ASSOCIATED WITH THE DEVELOPMENT OF MODERATE - SEVERE ENDOMETRIOSIS

Reproduction Fertility and Development ◽

10.1071/srb10abs135 ◽

2010 ◽

Vol 22 (9) ◽

pp. 53

Author(s):

G. W. Montgomery ◽

J. N. Painter ◽

C. A. Anderson ◽

D. R. Nyholt ◽

S. Macgregor ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Severe Disease ◽

Predictive Modelling ◽

Genome Wide Association ◽

Disease Stage ◽

Genome Wide ◽

A Genome ◽

Variation Explained ◽

The Uk

Endometriosis is a common gynaecological disease associated with severe pelvic pain and sub-fertility. There is considerable debate whether different endometriosis stages represent disease progression, or whether moderate-severe (rAFS III/IV) disease is pathological and minimal-mild (rAFS I/II) an epiphenomenon. We conducted a genome-wide association study using 540 082 SNPs in 3194 surgically confirmed endometriosis cases and 7060 controls from Australia and the UK. We used novel statistical methods to estimate the proportion of common variation explained by all markers and performed polygenic predictive modelling for disease stage, both showing significantly increased genetic loading among the 42% of cases with moderate-severe endometriosis. The strongest signals of association were also observed for moderate-severe disease. We subsequently genotyped 72 SNPs in an independent US dataset comprising 2392 endometriosis cases and 1646 controls. An association with rs7798431 on 7p15.2 for moderate-severe endometriosis (P = 6.0 × 10–8, OR = 1.34 (1.21–1.49)) was replicated, reaching combined genome-wide significance (P = 1.7 × 10–9; OR = 1.26 (1.17–1.35)). The implicated inter-genic region involves a 48 kb segment of high LD upstream of plausible candidate genes NFE2L3 and HOXA10. This locus is the first to be robustly implicated in the aetiology of endometriosis, with evidence of association limited to moderate-severe disease.

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

10.1101/217786 ◽

2017 ◽

Author(s):

Weihua Meng ◽

Mark J Adams ◽

Harry L Hebert ◽

Ian J Deary ◽

Andrew M McIntosh ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Genome Wide Association ◽

Uk Biobank ◽

Genetic Associations ◽

Psychological Traits ◽

Genome Wide ◽

A Genome ◽

The Uk

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.

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Chromosome 9p21 in sporadic amyotrophic lateral sclerosis in the UK and seven other countries: a genome-wide association study

The Lancet Neurology ◽

10.1016/s1474-4422(10)70197-6 ◽

2010 ◽

Vol 9 (10) ◽

pp. 986-994 ◽

Cited By ~ 151

Author(s):

Aleksey Shatunov ◽

Kin Mok ◽

Stephen Newhouse ◽

Michael E Weale ◽

Bradley Smith ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Sporadic Amyotrophic Lateral Sclerosis ◽

Chromosome 9P21 ◽

Genome Wide ◽

A Genome ◽

The Uk ◽

Lateral Sclerosis

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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.

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