Association of rare and common genetic variants in MOCOS with inadequate response to allopurinol.

Objectives: The minor allele of the common rs2231142 ABCG2 variant predicts inadequate response to allopurinol urate lowering therapy. We hypothesize that additional variants in genes encoding urate transporters and allopurinol-to-oxypurinol metabolic enzymes also predict allopurinol response.

Methods: This study included a subset of participants with gout from the Long-term Allopurinol Safety Study Evaluating Outcomes in Gout Patients (LASSO), whose whole genome was sequenced (n = 563).

Interaction of genetic variation at ADH1B and MLXIPL with alcohol consumption for elevated serum urate level and gout among people of European ethnicity.

Background: Alcohol consumption is a risk factor for hyperuricaemia and gout. Multiple single-nucleotide polymorphisms (SNPs) have been identified as associated with both alcohol consumption and serum urate or gout in separate genome-wide association studies (GWAS). This study aimed to identify and characterise interactions between these shared signals of genetic association and alcohol consumption for serum urate level, hyperuricaemia, and gout.

A Polynesianspecific missense CETP variant alters the lipid profile.

Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at associate with serum lipid profiles and cardiovascular disease. Here, sequencing of identified a missense variant rs1597000001 (p.

Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout.

Objective: To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout.

Methods: A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease.

Folic acid and methotrexate use and their association with COVID-19 diagnosis and mortality: a case-control analysis from the UK Biobank.

Objective: To determine if methotrexate or folic acid prescription was associated with differential risk for COVID-19 diagnosis or mortality.

Design: Case-control analysis.

Setting: The population-based UK Biobank (UKBB) cohort.

Change in serum urate level with urate-lowering therapy initiation associates in the immediate term with patient-reported outcomes in people with gout.

Objective: To examine the associations of changes in serum urate (SU) with health-related quality of life (HRQOL) in gout.

Methods: We used the first 6-months of data from four interventional trials and one observational, open-label study of urate-lowering therapy (ULT) use. HRQOL were assessed at baseline and every 3-months, and SU was measured monthly.

A Polynesian-specific copy number variant encompassing the MICA gene associates with gout.

Gout is of particularly high prevalence in the Māori and Pacific (Polynesian) populations of Aotearoa New Zealand (NZ). Here, we investigated the contribution of common population-specific copy number variation (CNV) to gout in the Aotearoa NZ Polynesian population. Microarray-generated genome-wide genotype data from Aotearoa NZ Polynesian individuals with (n = 1196) and without (n = 1249) gout were analyzed.

Gout and the risk of COVID-19 diagnosis and death in the UK Biobank: a population-based study.

Background: There is a paucity of data on outcomes for people with gout and COVID-19. We aimed to assess whether gout is a risk factor for diagnosis of COVID-19 and COVID-19-related death, and to test for sex- and drug-specific differences in risk.

Methods: We used data from the UK Biobank, which included 15 871 people with gout.

Mid-pass whole genome sequencing enables biomedical genetic studies of diverse populations.

Background: Historically, geneticists have relied on genotyping arrays and imputation to study human genetic variation. However, an underrepresentation of diverse populations has resulted in arrays that poorly capture global genetic variation, and a lack of reference panels. This has contributed to deepening global health disparities.

Factors associated with orthodontic pain.

Background: Pain experienced at teeth during orthodontic treatment varies largely over time, with the reasons for its interindividual variability being largely unknown: age, sex, clinical activations, psychosocial factors and genetic polymorphisms of candidate genes are putative factors that may account to explain this variability. We aimed to investigate the effect of clinical, demographic, psychological and genetic factors on pain levels experienced during fixed orthodontic treatment.

Methods: A convenience sample of 183 patients undergoing full-fixed orthodontic treatment were recruited.

Aotearoa New Zealand Māori and Pacific Population-amplified Gout Risk Variants: Is a Separate Risk Gene at the Locus.

Objective: The Māori and Pacific (Polynesian) population of Aotearoa New Zealand has a high prevalence of gout. Our aim was to identify potentially functional missense genetic variants in candidate inflammatory genes amplified in frequency that may underlie the increased prevalence of gout in Polynesian populations.

Methods: A list of 712 inflammatory disease-related genes was generated.

Gout, Rheumatoid Arthritis, and the Risk of Death Related to Coronavirus Disease 2019: An Analysis of the UK Biobank.

Objectives: The objectives for this study were to assess whether gout and/or rheumatoid arthritis (RA) are risk factors for coronavirus disease 2019 (COVID-19) diagnosis and to assess whether gout and/or RA are risk factors for death from COVID-19.

Methods: We used data from the UK Biobank. Multivariable-adjusted logistic regression was employed in the following analyses: analysis A, to test for association between gout and/or RA and COVID-19 diagnosis (n = 473,139); analysis B, to test for association between gout and/or RA and death from COVID-19 in a case-control cohort of people who died of or survived COVID-19 (n = 2059); analysis C, to test for association between gout and/or RA and death from COVID-19 in the entire UK Biobank cohort (n = 473,139).

The comparative effect of exposure to various risk factors on the risk of hyperuricaemia: diet has a weak causal effect.

Background: Prevention of hyperuricaemia (HU) is critical to the prevention of gout. Understanding causal relationships and relative contributions of various risk factors to hyperuricemia is therefore important in the prevention of gout. Here, we use attributable fraction to compare the relative contribution of genetic, dietary, urate-lowering therapy (ULT) and other exposures to HU.

Assessing the Relationship Between Serum Urate and Urolithiasis Using Mendelian Randomization: An Analysis of the UK Biobank.

Rationale & Objective: The association between hyperuricemia and urolithiasis has been previously reported. However, this association is based on observational data, which are prone to residual confounding. The aim of this work was to use Mendelian randomization (MR) to evaluate if this relationship represents a causal effect of hyperuricemia.

Genetic Polymorphisms on , and in Young Adults: Lack of Association With Alcohol Consumption.

Risk behaviors for young adults such as alcohol use are associated with increased risk of morbidity and mortality. Patterns of risk behavior may be genetically determined and vary between genders. Previous studies in both young adults and heavy drinking adult samples have demonstrated that some genotypes, such as A118G, Val158Met and Taq1A and C52IT, may predict addictive behaviors including alcohol consumption and impulsivity, although results have been mixed.

Common variants of EDA are associated with non-syndromic hypodontia.

Objective: The aim of this case-control study was to investigate the association between non-syndromic hypodontia and nineteen common variants of candidate genes ectodysplasin A (EDA), paired box 9 (PAX9), msh homeobox 1 (MSX1) and axis inhibition protein 2 (AXIN2).

Settings And Sample Population: Sixty-one hypodontia cases were frequency-matched to 253 controls with no missing teeth (excluding the third molars).

Material And Methods: Self-report data and DNA samples were collected from each participant.

Do Serum Urate-associated Genetic Variants Influence Gout Risk in People Taking Diuretics? Analysis of the UK Biobank.

Objective: The aim of this study was to determine whether serum urate (SU)-associated genetic variants differ in their influence on gout risk in people taking a diuretic compared to those not taking a diuretic.

Methods: This research was conducted using the UK Biobank Resource (n = 359,876). Ten SU-associated single-nucleotide polymorphisms (SNP) were tested for their association with gout according to diuretic use.

Functional Urate-Associated Genetic Variants Influence Expression of lincRNAs and .

Genetic variation in the genomic regulatory landscape likely plays a crucial role in the pathology of disease. Non-coding variants associated with disease can influence the expression of long intergenic non-coding RNAs (lincRNAs), which in turn function in the control of protein-coding gene expression. Here, we investigate the function of two independent serum urate-associated signals (SUA1 and SUA2) in close proximity to lincRNAs and an enhancer that reside ∼60 kb and ∼300 kb upstream of , respectively.

No causal effects of serum urate levels on the risk of chronic kidney disease: A Mendelian randomization study.

Background: Studies have shown strong positive associations between serum urate (SU) levels and chronic kidney disease (CKD) risk; however, whether the relation is causal remains uncertain. We evaluate whether genetic data are consistent with a causal impact of SU level on the risk of CKD and estimated glomerular filtration rate (eGFR).

Methods And Findings: We used Mendelian randomization (MR) methods to evaluate the presence of a causal effect.

Interactions between serum urate-associated genetic variants and sex on gout risk: analysis of the UK Biobank.

Background: Sex-specific differences in the effect of genetic variants on serum urate levels have been described. The aim of this study was to systematically examine whether serum urate-associated genetic variants differ in their influence on gout risk in men and women.

Methods: This research was conducted using the UK Biobank Resource.