Search

Your search keyword '"Williams, FMK"' showing total 6 results
Start Over Author "Williams, FMK" Topic polymorphism, single nucleotide
6 results on '"Williams, FMK"'

1. Genome-wide association study suggests that variation at the RCOR1 locus is associated with tinnitus in UK Biobank.

Author

Wells HRR, Abidin FNZ, Freidin MB, Williams FMK, and Dawson SJ

Subjects
Female, Humans, Male, Phenotype, Tinnitus pathology, Co-Repressor Proteins genetics, Nerve Tissue Proteins genetics, Polymorphism, Single Nucleotide, Tinnitus genetics
Abstract

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. From a total of 172,608 UK Biobank participants who answered questions on tinnitus we performed a case-control genome-wide association study for self-reported tinnitus. Final sample size used in association analysis was N = 91,424. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p = 1.7E-08), rs4900545 (p = 1.8E-08) and 14:103042287&#95;CT&#95;C (p = 3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p < 1E-06.

Published
2021
Full Text
View/download PDF

2. Disentangling the genetics of lean mass.

Author

Karasik D, Zillikens MC, Hsu YH, Aghdassi A, Akesson K, Amin N, Barroso I, Bennett DA, Bertram L, Bochud M, Borecki IB, Broer L, Buchman AS, Byberg L, Campbell H, Campos-Obando N, Cauley JA, Cawthon PM, Chambers JC, Chen Z, Cho NH, Choi HJ, Chou WC, Cummings SR, de Groot LCPGM, De Jager PL, Demuth I, Diatchenko L, Econs MJ, Eiriksdottir G, Enneman AW, Eriksson J, Eriksson JG, Estrada K, Evans DS, Feitosa MF, Fu M, Gieger C, Grallert H, Gudnason V, Lenore LJ, Hayward C, Hofman A, Homuth G, Huffman KM, Husted LB, Illig T, Ingelsson E, Ittermann T, Jansson JO, Johnson T, Biffar R, Jordan JM, Jula A, Karlsson M, Khaw KT, Kilpeläinen TO, Klopp N, Kloth JSL, Koller DL, Kooner JS, Kraus WE, Kritchevsky S, Kutalik Z, Kuulasmaa T, Kuusisto J, Laakso M, Lahti J, Lang T, Langdahl BL, Lerch MM, Lewis JR, Lill C, Lind L, Lindgren C, Liu Y, Livshits G, Ljunggren Ö, Loos RJF, Lorentzon M, Luan J, Luben RN, Malkin I, McGuigan FE, Medina-Gomez C, Meitinger T, Melhus H, Mellström D, Michaëlsson K, Mitchell BD, Morris AP, Mosekilde L, Nethander M, Newman AB, O'Connell JR, Oostra BA, Orwoll ES, Palotie A, Peacock M, Perola M, Peters A, Prince RL, Psaty BM, Räikkönen K, Ralston SH, Ripatti S, Rivadeneira F, Robbins JA, Rotter JI, Rudan I, Salomaa V, Satterfield S, Schipf S, Shin CS, Smith AV, Smith SB, Soranzo N, Spector TD, Stancáková A, Stefansson K, Steinhagen-Thiessen E, Stolk L, Streeten EA, Styrkarsdottir U, Swart KMA, Thompson P, Thomson CA, Thorleifsson G, Thorsteinsdottir U, Tikkanen E, Tranah GJ, Uitterlinden AG, van Duijn CM, van Schoor NM, Vandenput L, Vollenweider P, Völzke H, Wactawski-Wende J, Walker M, J Wareham N, Waterworth D, Weedon MN, Wichmann HE, Widen E, Williams FMK, Wilson JF, Wright NC, Yerges-Armstrong LM, Yu L, Zhang W, Zhao JH, Zhou Y, Nielson CM, Harris TB, Demissie S, Kiel DP, and Ohlsson C

Subjects
ADAMTS Proteins genetics, Absorptiometry, Photon, Adolescent, Adult, Aged, Aged, 80 and over, Alpha-Ketoglutarate-Dependent Dioxygenase FTO genetics, Electric Impedance, Extracellular Matrix Proteins genetics, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, RNA-Binding Proteins genetics, Receptor, Melanocortin, Type 4 genetics, Versicans genetics, White People genetics, Young Adult, Adipose Tissue metabolism, Body Composition genetics, Body Fluid Compartments metabolism, Muscle, Skeletal metabolism, Phenotype, Polymorphism, Single Nucleotide
Abstract

Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass., Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci., Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms)., Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection., Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

Published
2019
Full Text
View/download PDF

3. Association of Raynaud's phenomenon with a polymorphism in the NOS1 gene.

Author

Munir S, Freidin MB, Brain S, and Williams FMK

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Calcitonin Gene-Related Peptide genetics, Diseases in Twins, Female, Genetic Variation, Humans, Male, Middle Aged, Skin pathology, TRPA1 Cation Channel genetics, TRPM Cation Channels genetics, Temperature, Young Adult, Genetic Predisposition to Disease, Nitric Oxide Synthase Type I genetics, Polymorphism, Single Nucleotide, Raynaud Disease genetics
Abstract

Background: Raynaud's phenomenon (RP) describes the phenomenon of recurrent vasospasm of digital arteries, associated with skin colour changes: pallor, cyanosis and erythema. Twin studies have indicated a genetic predisposition for RP; however, the precise aetiology of RP remains unknown. It is thought that genetic variation in temperature-responsive or vasospastic genes might underlie RP so performed a candidate gene study in a large, population based sample. We assessed the association between RP and single nucleotide polymorphisms (SNPs) in the TRPA1, TRPM8, CALCA, CALCB and NOS1 genes., Methods: Analysis included a total of 4276 individuals from the TwinsUK database. RP status had been determined using validated, self-administered questionnaires and was diagnosed in 640 individuals (17.6%). 66 tag SNPs across the candidate genes were tested for association with RP status using a linear regression model, accounting for covariates. Adjustment was made for multiple testing. RegulomeDB and GTEx databases were used to assess possible functional effects of the polymorphisms., Results: Nominally significant associations between RP and four SNPs in NOS1 and one in CALCB were identified. After permutation testing, rs527590 SNP in NOS1 passed the significance threshold. RegulomeDB scores indicated an unlikely functional effect of this variant, while the survey of the GTEx database found the SNP and several variants in linkage disequilibrium to be cis-eQTLs in skin., Conclusion: Results indicate that RP is associated with variation in gene NOS1. This finding may be related to the observation that the significant SNP in NOS1 is known to exhibit functional influence on the gene expression.

Published
2018
Full Text
View/download PDF

4. An omics investigation into chronic widespread musculoskeletal pain reveals epiandrosterone sulfate as a potential biomarker.

Author

Livshits G, Macgregor AJ, Gieger C, Malkin I, Moayyeri A, Grallert H, Emeny RT, Spector T, Kastenmüller G, and Williams FMK

Subjects
Adult, Androsterone genetics, Body Mass Index, Female, Genomics, Germany epidemiology, Humans, Male, Mendelian Randomization Analysis, Musculoskeletal Pain epidemiology, Musculoskeletal Pain metabolism, Phenotype, Twins, Dizygotic genetics, Twins, Monozygotic genetics, United Kingdom epidemiology, Young Adult, Androsterone analogs & derivatives, Genome-Wide Association Study, Musculoskeletal Pain genetics, Polymorphism, Single Nucleotide genetics
Abstract

Chronic widespread musculoskeletal pain (CWP) is common, having a population prevalence of 10%. This study aimed to define the biological basis of the CWP/body mass association by using a systems biology approach. Adult female twins (n = 2444) from the TwinsUK registry who had extensive clinical, anthropometric, and "omic" data were included. Nontargeted metabolomics screening including 324 metabolites was carried out for CWP and body composition using dual-energy X-ray absorptiometry. The biological basis of these associations was explored through a genome-wide association study and replicated in an independent population sample (Cooperative Health Research in the Region of Augsburg [KORA] study, n = 2483). A causal role for the genetic variants identified was sought in CWP using a Mendelian randomisation study design. Fat mass/height2 was the body composition variable most strongly associated with CWP (TwinsUK: P = 2.4 × 10(-15) and KORA: P = 1.59 × 10(-10)). Of 324 metabolites examined, epiandrosterone sulfate (EAS) was highly associated with both CWP (P = 1.05 × 10(-09) in TwinsUK and P = 3.70 × 10(-06) in KORA) and fat mass/height2. Genome-wide association study of EAS identified imputed single nucleotide polymorphism rs1581492 at 7q22.1 to be strikingly associated with EAS levels (P ≤ 2.49 × 10(-78)), and this result was replicated in KORA (P = 2.12 × 10(-9)). Mendelian randomization by rs1581492 genotype showed that EAS is unlikely to be causally related to CWP. Using an agnostic omics approach to focus on the association of CWP with body mass index, we have confirmed a steroid hormone association and identified a genetic variant upstream of the CYP genes, which likely controls this response. This study suggests that steroid hormone abnormalities result from pain rather than causing it, and EAS may provide a biomarker that identifies subgroups at risk of CWP.

Published
2015
Full Text
View/download PDF

5. Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease

Author

Song, C, Burgess, S, Eicher, JD, O'Donnell, CJ, Johnson, AD, Huang, J, Sabater-Lleal, M, Asselbergs, FW, Tregouet, D, Shin, SY, Ding, J, Baumert, J, Oudot-Mellakh, T, Folkersen, L, Smith, NL, Williams, SM, Ikram, MA, Kleber, ME, Becker, DM, Truong, V, Mychaleckyj, JC, Tang, W, Yang, Q, Sennblad, B, Moore, JH, Williams, FMK, Dehghan, A, Silbernagel, G, Schrijvers, EMC, Smith, S, Karakas, M, Tofler, GH, Silveira, A, Navis, GJ, Lohman, K, Chen, MH, Peters, A, Goel, A, Hopewell, JC, Chambers, JC, Saleheen, D, Lundmark, P, Psaty, BM, Strawbridge, RJ, Boehm, BO, Carter, AM, Meisinger, C, Peden, JF, Bis, JC, McKnight, B, Öhrvik, J, Taylor, K, Franzosi, MG, Seedorf, U, Collins, R, Franco-Cereceda, A, Syvänen, AC, Goodall, AH, Yanek, LR, Cushman, M, Müller-Nurasyid, M, Folsom, AR, Basu, S, Matijevic, N, Van Gilst, WH, Kooner, JS, Danesh, J, Clarke, R, Meigs, JB, Kathiresan, S, Reilly, MP, Klopp, N, Harris, TB, Winkelmann, BR, Grant, PJ, Hillege, HL, Watkins, H, Spector, TD, Becker, LC, Tracy, RP, März, W, Uitterlinden, AG, Eriksson, P, Cambien, F, Morange, PE, Koenig, W, Soranzo, N, Van der Harst, P, Liu, Y, Hamsten, A, Ehret, GB, Munroe, PB, Rice, KM, Bochud, M, Chasman, DI, Smith, AV, Epidemiology, Internal Medicine, Radiology & Nuclear Medicine, Virology, Clinical Genetics, Obstetrics & Gynecology, and Gastroenterology & Hepatology

Subjects
0301 basic medicine, Blood Glucose, Aging, Cardiac & Cardiovascular Systems, Epidemiology, medicine.medical_treatment, Genome-wide association study, Coronary Disease, Review, Coronary Artery Disease, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, Cardiovascular, chemistry.chemical_compound, 0302 clinical medicine, Risk Factors, single nucleotide polymorphism, GENETIC-VARIANTS, Odds Ratio, ARTERY-DISEASE, METABOLIC SYNDROME, genome‐wide association study, INSULIN-RESISTANCE, education.field_of_study, Systematic Review and Meta‐Analysis, Fibrinolysis, Incidence, Mendelian Randomization Analysis, Single Nucleotide, C-REACTIVE PROTEIN, 3. Good health, Observational Studies as Topic, plasminogen activator inhibitor type 1, Heart Disease, CARDIOVASCULAR-DISEASE, Plasminogen activator inhibitor-1, Cardiology, Cardiology and Cardiovascular Medicine, Risk assessment, Lipoproteins, HDL, Life Sciences & Biomedicine, medicine.medical_specialty, HDL, Lipoproteins, Population, Polymorphism, Single Nucleotide, Risk Assessment, 03 medical and health sciences, Genetic, Association Studies, Clinical Research, Internal medicine, Mendelian randomization, Plasminogen Activator Inhibitor 1, Journal Article, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Polymorphism, coronary heart disease, education, Heart Disease - Coronary Heart Disease, Science & Technology, genome-wide association study, business.industry, coronary heart disease ■ genome‐wide association study ■ Mendelian randomization ■ plasminogen activator inhibitor type 1 ■ single nucleotide polymorphism, Odds ratio, SUMMARIZED DATA, 030104 developmental biology, Endocrinology, MYOCARDIAL-INFARCTION, chemistry, Multivariate Analysis, Cardiovascular System & Cardiology, business, Biomarkers, Genome-Wide Association Study
Abstract

Background Plasminogen activator inhibitor type 1 ( PAI ‐1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI ‐1 levels are associated with increased risk of coronary heart disease ( CHD ). However, it is unclear whether the association reflects a causal influence of PAI ‐1 on CHD risk. Methods and Results To evaluate the association between PAI ‐1 and CHD , we applied a 3‐step strategy. First, we investigated the observational association between PAI ‐1 and CHD incidence using a systematic review based on a literature search for PAI ‐1 and CHD studies. Second, we explored the causal association between PAI ‐1 and CHD using a Mendelian randomization approach using summary statistics from large genome‐wide association studies. Finally, we explored the causal effect of PAI ‐1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta‐analysis, the highest quantile of blood PAI ‐1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age‐ and sex‐adjusted model. The effect size was reduced in studies using a multivariable‐adjusted model (odds ratio=1.46; 95% CI : 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI ‐1 level on CHD risk (odds ratio=1.22 per unit increase of log‐transformed PAI ‐1; 95% CI : 1.01, 1.47). In addition, we also detected a causal effect of PAI ‐1 on elevating blood glucose and high‐density lipoprotein cholesterol. Conclusions Our study indicates a causal effect of elevated PAI ‐1 level on CHD risk, which may be mediated by glucose dysfunction.

Published
2017

6. Genome-wide association study meta-analysis of chronic widespread pain: evidence for involvement of the 5p15.2 region

Author

Peters, Marjolein, Broer, Linda, Willemen, HLDM, Eiriksdottir, G, Hocking, LJ, Holliday, KL, Horan, MA, Meulenbelt, I, Neogi, T, Popham, M, Schmidt, CO, Soni, A, Valdes, AM, Amin, Najaf, Dennison, EM, Eijkelkamp, N, Harris, TB, Hart, DJ, Hofman, Bert, Huygen, Frank, Jameson, KA, Jones, GT, Launer, LJ (Lenore), Kerkhof, HJM, Kruijf, Marjolein, McBeth, J, Kloppenburg, M, Ollier, WE, Oostra, Ben, Payton, A, Rivadeneira, Fernando, Smith, BH, Smith, AV, Stolk, Lisette, Teumer, A, Thomson, W, Uitterlinden, André, Wang, K, Wingerden, Sophie, Arden, NK, Cooper, C, Felson, D, Gudnason, V, Macfarlane, GJ, Pendleton, N, Slagboom, PE (Eline), Spector, TD, Volzke, H, Kavelaars, A, Duijn, Cornelia, Williams, FMK, van Meurs, Joyce, Internal Medicine, Epidemiology, Anesthesiology, and Clinical Genetics

Subjects
Genotype, Epidemiology, Fibromyalgis/Pain Syndromes, Polymorphism, Single Nucleotide, Disease Models, Animal, Mice, Gene Polymorphism, Animals, Chromosomes, Human, Pair 5, Humans, Female, Genetic Predisposition to Disease, Chronic Pain, Basic and Translational Research, Genome-Wide Association Study
Abstract

BACKGROUND AND OBJECTIVES: Chronic widespread pain (CWP) is a common disorder affecting ∼10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP. METHODS: We conducted a GWAS meta-analysis in 1308 female CWP cases and 5791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1480 CWP cases and 7989 controls. Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain. RESULTS: The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of chaperonin-containing-TCP1-complex-5 gene (CCT5) and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (minor allele frequency=43%; OR=1.30, 95% CI 1.19 to 1.42, p=1.2×10(-8)). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95% CI 1.10 to 1.24, p=4.7×10(-7)) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95% CI 1.14 to 1.32, p=3.4×10(-8), I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (p>7.7×10(-4)). CONCLUSIONS: We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.

Published
2012

Catalog

Books, media, physical & digital resources
See catalog results