Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain

Background and objectivesChronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48%–54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP.MethodsNorthern Europeans from UK Biobank comprising 6914 cases reporting pain all over the body lasting >3 months and 242 929 controls were studied. Replication of three independent genome-wide significant single nucleotide polymorphisms was attempted in six independent European cohorts (n=43 080; cases=14 177). Genetic correlations with risk factors, tissue specificity and colocalisation were examined.ResultsThree genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes Ring Finger Protein 123 (RNF123), ATPase secretory pathway Ca2+transporting 1 (ATP2C1) and catechol-O-methyltransferase (COMT). The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227) and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth and years of schooling were identified. Tissue specificity and colocalisation analysis highlight the relevance of skeletal muscle in CWP.ConclusionsWe report a novel association of RNF123 locus and a suggestive association of ATP2C1 locus with CWP. Both loci are consistent with a role of calcium regulation in CWP. The association with COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.

Download Full-text

Genome-wide association study identifies RNF123 locus as associated with chronic widespread musculoskeletal pain

10.1101/2020.11.30.20241000 ◽

2020 ◽

Author(s):

Md Shafiqur Rahman ◽

Bendik S Winsvold ◽

S.O. Chavez Chavez ◽

Sigrid Børte ◽

Yakov A. Tsepilov ◽

...

Keyword(s):

Association Study ◽

Genetic Correlation ◽

Musculoskeletal Pain ◽

Tissue Specificity ◽

Genome Wide Association Study ◽

The Body ◽

Genome Wide Association ◽

List Type ◽

Genome Wide

AbstractBackground and ObjectivesChronic widespread musculoskeletal pain (CWP) is a symptom of fibromyalgia and a complex trait with poorly understood pathogenesis. CWP is heritable (48-54%), but its genetic architecture is unknown and candidate gene studies have produced inconsistent results. We conducted a genome-wide association study to get insight into the genetic background of CWP.MethodsNorthern Europeans from UK Biobank comprising 6,914 cases reporting pain all over the body lasting more than 3 months and 242,929 controls were studied. Replication of three lead genome-wide significant single nucleotide polymorphisms (SNPs) was attempted in 6 independent European cohorts (N=43,080; cases=14,177). Genetic correlations with risk factors, tissue specificity, and colocalization were examined.ResultsThree genome-wide significant loci were identified (rs1491985, rs10490825, rs165599) residing within the genes RNF123, ATP2C1, and COMT. The RNF123 locus was replicated (meta-analysis p=0.0002), the ATP2C1 locus showed suggestive association (p=0.0227), and the COMT locus was not replicated. Partial genetic correlation between CWP and depressive symptoms, body mass index, age of first birth, and years of schooling were identified. Tissue specificity and colocalization analysis highlight the relevance of skeletal muscle in CWP.ConclusionsWe report a novel association of RNF123 locus with CWP and suggest a role of ATP2C1, consistent with a role of calcium regulation in CWP. The association to COMT, one of the most studied genes in chronic pain field, was not confirmed in the replication analysis.Key messagesWhat is already known about this subject?Chronic widespread musculoskeletal pain (CWP) is a primary diagnostic feature of fibromyalgia.CWP is moderately heritable, but precise genes involved in the pathogenesis of CWP are yet to be identified.What does this study add?This is the largest genetic study conducted on CWP to date and identified novel genetic risk loci (RNF123 and ATP2C1).The genetic signal points to peripheral pain mechanisms in CWP, and shows genetic correlation with other traits, including BMI and depression.How might this impact on clinical practice or future developments?The findings add to etiological basis of CWP.

Download Full-text

Genome-wide association study reveals sex-specific genetic architecture of facial attractiveness

10.1101/339226 ◽

2018 ◽

Author(s):

Bowen Hu ◽

Ning Shen ◽

James J. Li ◽

Hyunseung Kang ◽

Jinkuk Hong ◽

...

Keyword(s):

Association Study ◽

Genetic Architecture ◽

Genetic Basis ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Facial Attractiveness ◽

Genome Wide Association ◽

Hormone Synthesis ◽

Genome Wide ◽

A Genome

AbstractFacial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 3,928 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci and highlighted a handful of candidate genes, many of which are specifically expressed in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.

Download Full-text

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.

Download Full-text

Genome-wide association study of self-reported walking pace suggests beneficial effects of brisk walking on health and survival

Communications Biology ◽

10.1038/s42003-020-01357-7 ◽

2020 ◽

Vol 3 (1) ◽

Author(s):

Iain R. Timmins ◽

Francesco Zaccardi ◽

Christopher P. Nelson ◽

Paul W. Franks ◽

Thomas Yates ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Strong Predictor ◽

Genetic Correlations ◽

Causal Link ◽

Genome Wide Association ◽

European Ancestry ◽

Beneficial Effects ◽

Genome Wide ◽

A Genome

AbstractWalking is a simple form of exercise, widely promoted for its health benefits. Self-reported walking pace has been associated with a range of cardiorespiratory and cancer outcomes, and is a strong predictor of mortality. Here we perform a genome-wide association study of self-reported walking pace in 450,967 European ancestry UK Biobank participants. We identify 70 independent associated loci (P < 5 × 10−8), 11 of which are novel. We estimate the SNP-based heritability as 13.2% (s.e. = 0.21%), reducing to 8.9% (s.e. = 0.17%) with adjustment for body mass index. Significant genetic correlations are observed with cardiometabolic, respiratory and psychiatric traits, educational attainment and all-cause mortality. Mendelian randomization analyses suggest a potential causal link of increasing walking pace with a lower cardiometabolic risk profile. Given its low heritability and simple measurement, these findings suggest that self-reported walking pace is a pragmatic target for interventions aiming for general benefits on health.

Download Full-text

The Genetic Structure of Pain in Depression Patients: A Genome-Wide Association Study and Proteome-Wide Association Study

10.21203/rs.3.rs-1210160/v1 ◽

2022 ◽

Author(s):

Zhen Zhang ◽

Li Liu ◽

Huijie Zhang ◽

Chun'e Li ◽

Yujing Chen ◽

...

Keyword(s):

Association Study ◽

Genetic Correlation ◽

Candidate Genes ◽

Genome Wide Association Study ◽

Genetic Correlations ◽

Gene Set Enrichment Analysis ◽

Genome Wide Association ◽

Post Traumatic Stress ◽

Genome Wide ◽

A Genome

Abstract Background Pain symptoms are common in the patients with depression. Comparing with the general population, the pain in depression patients has more complex biological mechanism. We aim to explore the etiological mechanism of pain in depression patients from the perspective of genetics. Methods Utilizing the UK Biobank samples with self-reported depression status or PHQ score ≥10, we conducted genome-wide association study (GWAS) of seven pain traits (N=1,133-58,349). The GWAS summary were then integrated with two different reference protein weights (ROS/MAP and Banner) for proteome-wide association study (PWAS) using the FUSION pipeline. Additionally, LDSC analysis was performed to explore the genetic correlation between pain traits in depression patients and common psychiatry disorders. And biological processes and functions that related to pain associated genes in depression patients were analyzed by gene set enrichment analysis. Results GWAS identified 3 significant genes associated with different pain traits in depression patients, including TRIOBP (PGWAS= 4.48× 10−8) for stomach or abdominal pain, SLC9A9(PGWAS= 2.77× 10−8) for multisite chronic pain (MCP) and ADGRF1 (PGWAS= 1.51× 10−8) for neck or shoulder pain. PWAS also identified multiple candidate genes associated with different pain traits in depression patients, such as TPRG1L (permutation-based PPWAS−Banner= 3.38× 10−2) and SIRPA (permutation-based PPWAS−Banner= 3.65×10−2) for MCP etc. LDSC analysis results showed that MCP was positively correlated with attention-deficit hyperactivity disorder (ADHD) (genetic correlation(rg) = 0.123, PLDSC = 0.039) and post-traumatic stress disorder (PTSD) (rg = 0.217, PLDSC = 0.029). Conclusions We reported multiple novel candidate genes and genetic correlations for pain traits in depression patients, providing novel clues for understanding the genetic mechanisms underlying the pain in depression patients.

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