APOL1 Risk Variants Associated with Serum Albumin in a Population-Based Cohort Study.

INTRODUCTION: The association of apolipoprotein L1 (APOL1) nephropathy risk variants (APOL1), unique to African-ancestry (African-American [AA]) populations, with systemic inflammation, a contributor to chronic kidney disease (CKD) and end-stage kidney disease (ESKD) is ill-defined. This study aimed to describe the role of inflammatory markers in the relationship between APOL1 and incident kidney outcomes using a prospective cohort study. METHODS: APOL1 high-risk status under a recessive genetic model was studied in 10,605 AA adults aged ≥45 years from the Reasons for Geographic and Racial Differences in Stroke study. The primary variables of interest were inflammatory markers: C-reactive protein (mg/dL), white blood cell count (cells/mm3), and serum albumin (sALB) (mg/dL). High inflammation status was defined if at least one of these inflammatory markers exceeded clinical threshold. The association between APOL1 and biomarkers were assessed using regression models adjusting for age, sex, ancestry, hypertension, lipid medications, albumin-to-creatinine ratio, and estimated glomerular filtration rate (eGFR). Models were stratified by diabetes status. We identified incident ESKD using USRDS linkage, and we defined incident CKD as an eGFR <60 mL/min/1.73 m2 and ≥25% decline in the eGFR and normal baseline eGFR and tested for mediation of APOL1 and outcomes by biomarkers using the causal inference approach. RESULTS: Among 7,151 participants with data available on all inflammation markers, 4,479 participants had ≥1 marker meeting the clinical threshold. APOL1 high-risk status was associated with lower adjusted odds of reduced sALB {odds ratio (OR) (95% confidence interval [CI]): 0.59 [0.36, 0.96])}, and this association was significant in people with diabetes (OR [95% CI]: 0.40 [0.18, 0.89]) but not in those without diabetes. There was no association of APOL1 high-risk status with other markers or high inflammation status. APOL1 was independently associated with ESKD (OR [95% CI] = 1.78 [1.28, 2.48]) and CKD (OR [95% CI] = 1.38 [1.00, 1.91]). On mediation analysis, the direct effect between APOL1 and ESKD strengthened after accounting for sALB, but the estimated mediated effect was not statistically significant (OR [95% CI]: 0.98 [0.92, 1.05], p = 0.58). CONCLUSION: APOL1 high-risk variants were associated with sALB. However, sALB did not statistically mediate the association between APOL1 and incident ESKD.

Genetic influences on susceptibility to rheumatoid arthritis in African-Americans.

Large meta-analyses of rheumatoid arthritis (RA) susceptibility in European (EUR) and East Asian (EAS) populations have identified >100 RA risk loci, but genome-wide studies of RA in African-Americans (AAs) are absent. To address this disparity, we performed an analysis of 916 AA RA patients and 1392 controls and aggregated our data with genotyping data from >100 000 EUR and Asian RA patients and controls. We identified two novel risk loci that appear to be specific to AAs: GPC5 and RBFOX1 (PAA < 5 × 10-9). Most RA risk loci are shared across different ethnicities, but among discordant loci, we observed strong enrichment of variants having large effect sizes. We found strong evidence of effect concordance for only 3 of the 21 largest effect index variants in EURs. We used the trans-ethnic fine-mapping algorithm PAINTOR3 to prioritize risk variants in >90 RA risk loci. Addition of AA data to those of EUR and EAS descent enabled identification of seven novel high-confidence candidate pathogenic variants (defined by posterior probability > 0.8). In summary, our trans-ethnic analyses are the first to include AAs, identified several new RA risk loci and point to candidate pathogenic variants that may underlie this common autoimmune disease. These findings may lead to better ways to diagnose or stratify treatment approaches in RA.

The scope and severity of white-nose syndrome on hibernating bats in North America.

Assessing the scope and severity of threats is necessary for evaluating impacts on populations to inform conservation planning. Quantitative threat assessment often requires monitoring programs that provide reliable data over relevant spatial and temporal scales, yet such programs can be difficult to justify until there is an apparent stressor. Leveraging efforts of wildlife management agencies to record winter counts of hibernating bats, we collated data for 5 species from over 200 sites across 27 U.S. states and 2 Canadian provinces from 1995 to 2018 to determine the impact of white-nose syndrome (WNS), a deadly disease of hibernating bats. We estimated declines of winter counts of bat colonies at sites where the invasive fungus that causes WNS (Pseudogymnoascus destructans) had been detected to assess the threat impact of WNS. Three species undergoing species status assessment by the U.S. Fish and Wildlife Service (Myotis septentrionalis, Myotis lucifugus, and Perimyotis subflavus) declined by more than 90%, which warrants classifying the severity of the WNS threat as extreme based on criteria used by NatureServe. The scope of the WNS threat as defined by NatureServe criteria was large (36% of Myotis lucifugus range) to pervasive (79% of Myotis septentrionalis range) for these species. Declines for 2 other species (Myotis sodalis and Eptesicus fuscus) were less severe but still qualified as moderate to serious based on NatureServe criteria. Data-sharing across jurisdictions provided a comprehensive evaluation of scope and severity of the threat of WNS and indicated regional differences that can inform response efforts at international, national, and state or provincial jurisdictions. We assessed the threat impact of an emerging infectious disease by uniting monitoring efforts across jurisdictional boundaries and demonstrated the importance of coordinated monitoring programs, such as the North American Bat Monitoring Program (NABat), for data-driven conservation assessments and planning.

Alcance y Severidad del Síndrome de Nariz Blanca en los Murciélagos Hibernando en América del Norte Resumen La evaluación del alcance y la severidad de las amenazas es necesaria para los análisis de impacto sobre las poblaciones que se usan para orientar a la planeación de la conservación. La evaluación cuantitativa de amenazas con frecuencia requiere de programas de monitoreo que proporcionen datos confiables en escalas espaciales y temporales, aunque dichos programas pueden ser difíciles de justificar hasta que exista un estresante aparente. Gracias a una movilización de esfuerzos de las agencias de manejo de fauna para registrar los conteos invernales de murciélagos hibernadores, recopilamos datos para cinco especies en más de 200 sitios a lo largos de 27 estados de EUA y dos provincias canadienses entre 1995 y 2018 para determinar el impacto del síndrome de nariz blanca (SNB), una enfermedad mortal de los murciélagos hibernadores. Estimamos declinaciones en los conteos invernales de las colonias de murciélagos en sitios en donde el hongo invasivo que ocasiona el SNB (Pseudogymnoascus destructans) había sido detectado para evaluar el impacto de amenaza del SNB. Tres especies que se encuentran bajo valoración por parte del Servicio de Pesca y Vida Silvestre de los EUA (Myotis septentrionalis, Myotis lucifugus y Perimyotis subflavus) tuvieron una declinación de más del 90%, lo que justifica la clasificación de la severidad de la amenaza del SNB como extrema con base en el criterio usado por NatureServe. El alcance de la amenaza del SNB definido por el criterio de NatureServe fue desde amplio (36% de la distribución de Myotis lucifugus) hasta dominante (79% de la distribución de Myotis septentrionalis) para estas especies. Las declinaciones de otras dos especies (Myotis sodalis y Eptesicus fuscus) fueron menos severas, pero de igual manera quedaron clasificadas desde moderada hasta seria con base en los criterios de NatureServe. El intercambio de datos entre las jurisdicciones proporcionó una evaluación completa del alcance y la severidad de la amenaza del SNB e indicó las diferencias regionales que pueden guiar a los esfuerzos de respuesta realizados en las jurisdicciones internacionales, nacionales, estatales o provinciales. Evaluamos el impacto de amenaza de una enfermedad infecciosa emergente mediante la combinación de los esfuerzos de monitoreo que sobrepasan fronteras jurisdiccionales y demostramos la importancia que tienen para la planeación y la evaluación basadas en datos de la conservación los programas de monitoreo coordinados, como el Programa de Monitoreo de los Murciélagos Norteamericanos (NABat).

Comorbidities in gout and hyperuricemia: causality or epiphenomena?

PURPOSE OF REVIEW: To review advances in the understanding of potentially causal relationships between gout, hyperuricemia and comorbidities. RECENT FINDINGS: Observational studies reveal 4-5 comorbidity clusters in gout patients. There tend to be gout alone, gout with chronic kidney disease and gout with other metabolic comorbidities. However, heterogeneous study populations and confounding make inference difficult for causal relationships. Mendelian randomization leverages genetic information as an instrumental variable to indicate putatively causal relationships between traits of epidemiological interest. Thus far, Mendelian randomization has not indicated widespread causal relationships of serum urate for comorbid traits. However, BMI has a small causal effect on serum urate, which may partially explain the increased prevalence of metabolic syndrome and cardiovascular disease among those with gout and hyperuricemia. There is a lack of robust and sufficiently powered Mendelian randomization studies for many serum urate-associated traits, such as hypertension. No adequately powered studies have been completed for gout and its comorbidities. SUMMARY: Although observational studies indicate putative causal effects of serum urate on comorbidities, Mendelian randomization studies suggest that serum urate does not have a causal role on the various tested comorbidities. There remains work to be done in clarifying the causal role of gout per se on the same traits.

Dense Genotyping of Immune-Related Regions Identifies Loci for Rheumatoid Arthritis Risk and Damage in African Americans.

Over 100 risk loci for rheumatoid arthritis (RA) have been identified in individuals of European and Asian descent, but the genetic basis for RA in African Americans is less well understood. We genotyped 610 African Americans with autoantibody positive RA and 933 African American controls on the ImmunoChip (iChip) array. Using multivariable regression we evaluated the association between iChip markers and the risk of RA and radiographic severity. The single nucleotide polymorphism (SNP) rs1964995 (OR = 1.97, p = 1.28 × 10-15) near HLA-DRB1 was the most strongly associated risk SNP for RA susceptibility; SNPs in AFF3, TNFSF11, and TNFSF18 loci were suggestively associated (10-4 < p < 3.1 × 10-6). Trans-ethnic fine mapping of AFF3 identified a 90% credible set containing previously studied variants including rs9653442, rs7608424, and rs6712515 as well as the novel candidate variant rs11681966; several of these likely influence AFF3 gene expression level. Variants in TNFRSF9, CTLA4, IL2RA, C5/TRAF1, and ETS1 - but no variants within the major histocompatibility complex - were associated with RA radiographic severity. Conditional regression and pairwise linkage disequilibrium (LD) analyses suggest that additional pathogenic variants may be found in ETS1 and IL2RA beyond those found in other ethnicities. In summary, we use the dense genotyping of the iChip array and unique LD structure of African Americans to validate known risk loci for RA susceptibility and radiographic severity, and to better characterize the associations of AFF3, ETS1, and IL2RA.

Serum urate gene associations with incident gout, measured in the Framingham Heart Study, are modified by renal disease and not by body mass index.

We hypothesized that serum urate-associated SNPs, individually or collectively, interact with BMI and renal disease to contribute to risk of incident gout. We measured the incidence of gout and associated comorbidities using the original and offspring cohorts of the Framingham Heart Study. We used direct and imputed genotypes for eight validated serum urate loci. We fit binomial regression models of gout incidence as a function of the covariates, age, type 2 diabetes, sex, and all main and interaction effects of the eight serum urate SNPs with BMI and renal disease. Models were also fit with a genetic risk score for serum urate levels which corresponds to the sum of risk alleles at the eight SNPs. Model covariates, age (P = 5.95E-06), sex (P = 2.46E-39), diabetes (P = 2.34E-07), BMI (P = 1.14E-11) and the SNPs, rs1967017 (P = 9.54E-03), rs13129697 (P = 4.34E-07), rs2199936 (P = 7.28E-03) and rs675209 (P = 4.84E-02) were all associated with incident gout. No BMI by SNP or BMI by serum urate genetic risk score interactions were statistically significant, but renal disease by rs1106766 was statistically significant (P = 6.12E-03). We demonstrated that minor alleles of rs1106766 (intergenic, INHBC) were negatively associated with the risk of incident gout in subjects without renal disease, but not for individuals with renal disease. These analyses demonstrate that a significant component of the risk of gout may involve complex interplay between genes and environment.

Simple regression for correcting ΔCt bias in RT-qPCR low-density array data normalization.

BACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) is considered the gold standard for quantifying relative gene expression. Normalization of RT-qPCR data is commonly achieved by subtracting the Ct values of the internal reference genes from the Ct values of the target genes to obtain ΔCt. ΔCt values are then used to derive ΔΔCt when compared to a control group or to conduct further statistical analysis. RESULTS: We examined two rheumatoid arthritis RT-qPCR low density array datasets and found that this normalization method introduces substantial bias due to differences in PCR amplification efficiency among genes. This bias results in undesirable correlations between target genes and reference genes, which affect the estimation of fold changes and the tests for differentially expressed genes. Similar biases were also found in multiple public mRNA and miRNA RT-qPCR array datasets we analysed. We propose to regress the Ct values of the target genes onto those of the reference genes to obtain regression coefficients, which are then used to adjust the reference gene Ct values before calculating ΔCt. CONCLUSIONS: The per-gene regression method effectively removes the ΔCt bias. This method can be applied to both low density RT-qPCR arrays and individual RT-qPCR assays.

Use of a multiethnic approach to identify rheumatoid- arthritis-susceptibility loci, 1p36 and 17q12.

We have previously shown that rheumatoid arthritis (RA) risk alleles overlap between different ethnic groups. Here, we utilize a multiethnic approach to show that we can effectively discover RA risk alleles. Thirteen putatively associated SNPs that had not yet exceeded genome-wide significance (p < 5 × 10(-8)) in our previous RA genome-wide association study (GWAS) were analyzed in independent sample sets consisting of 4,366 cases and 17,765 controls of European, African American, and East Asian ancestry. Additionally, we conducted an overall association test across all 65,833 samples (a GWAS meta-analysis plus the replication samples). Of the 13 SNPs investigated, four were significantly below the study-wide Bonferroni corrected p value threshold (p < 0.0038) in the replication samples. Two SNPs (rs3890745 at the 1p36 locus [p = 2.3 × 10(-12)] and rs2872507 at the 17q12 locus [p = 1.7 × 10(-9)]) surpassed genome-wide significance in all 16,659 RA cases and 49,174 controls combined. We used available GWAS data to fine map these two loci in Europeans and East Asians, and we found that the same allele conferred risk in both ethnic groups. A series of bioinformatic analyses identified TNFRSF14-MMEL1 at the 1p36 locus and IKZF3-ORMDL3-GSDMB at the 17q12 locus as the genes most likely associated with RA. These findings demonstrate empirically that a multiethnic approach is an effective strategy for discovering RA risk loci, and they suggest that combining GWASs across ethnic groups represents an efficient strategy for gaining statistical power.

Immunochip identifies novel, and replicates known, genetic risk loci for rheumatoid arthritis in black South Africans.

The aim of this study was to identify genetic variants associated with rheumatoid arthritis (RA) risk in black South Africans. Black South African RA patients (n = 263) were compared with healthy controls (n = 374). Genotyping was performed using the Immunochip, and four-digit high-resolution human leukocyte antigen (HLA) typing was performed by DNA sequencing of exon 2. Standard quality control measures were implemented on the data. The strongest associations were in the intergenic region between the HLA-DRB1 and HLA-DQA1 loci. After conditioning on HLA-DRB1 alleles, the effect in the rest of the extended major histocompatibility (MHC) diminished. Non-HLA single nucleotide polymorphisms (SNPs) in the intergenic regions LOC389203|RBPJ, LOC100131131|IL1R1, KIAA1919|REV3L, LOC643749|TRAF3IP2, and SNPs in the intron and untranslated regions (UTR) of IRF1 and the intronic region of ICOS and KIAA1542 showed association with RA (p < 5 × 10(-5)). Of the SNPs previously associated with RA in Caucasians, one SNP, rs874040, locating to the intergenic region LOC389203|RBPJ was replicated in this study. None of the variants in the PTPN22 gene was significantly associated. The seropositive subgroups showed similar results to the overall cohort. The effects observed across the HLA region are most likely due to HLA-DRB1, and secondary effects in the extended MHC cannot be detected. Seven non-HLA loci are associated with RA in black South Africans. Similar to Caucasians, the intergenic region between LOC38920 and RBPJ is associated with RA in this population. The strong association of the R620W variant of the PTPN22 gene with RA in Caucasians was not replicated since this variant was monomorphic in our study, but other SNP variants of the PTPN22 gene were also not associated with RA in black South Africans, suggesting that this locus does not play a major role in RA in this population.

A RANGE-WIDE ECTOPARASITE SURVEY FOR ALLEGHENY WOODRATS (NEOTOMA MAGISTER).

Allegheny woodrats (Neotoma magister) are karst-specializing rodents that are rare or in conservation need in many states within their current range. Parasitism and habitat fragmentation have been suggested as primary reasons for declining populations. The presence, prevalence, and impact of ectoparasites, including fleas, ticks, and bots, is not fully understood rangewide. We collected Allegheny woodrat ectoparasites across 8 states in their range, identifying parasites via morphological and genetic means. Across contributions from 8 states, we discovered 2 woodrat-specific fleas parasitizing Allegheny woodrats: Orchopeas pennsylvanicus (all contributing states, n = 228) and Epitedia cavernicola (Indiana only, n = 9). The former was a new state record in New Jersey and Ohio. Woodrat specialists Ixodes woodi were morphologically identified as the dominant tick species (n = 38), and our contributions to genetic databases may ease confusion in future efforts. Three generalist species of ticks representing 8 individuals were identified as Dermacentor variabilis, Amblyomma americanum, and Ixodes scapularis. Only 2 bot fly species were recognized in Allegheny woodrats: 1 squirrel bot (Cuterebra emasculator) and 10 individuals of Cuterebra sp. not genetically conspecific to any known eastern U.S. rodent bot. The host specificity for fleas is not surprising, given that previous small-scale surveys and ticks primarily appear to be a mix of genus-specific (Ixodes woodi) and generalist species. There remains uncertainty with bots via morphological and genetic analyses. Our survey presents a wide-ranging baseline survey for Allegheny woodrats across their range, emphasizing the diversity (or specificity) of parasite groups for this species. An understanding of Allegheny woodrats and the health impact of ectoparasites is imperative because they face myriad challenges rangewide, especially considering the bot-driven demise of 1 woodrat in our study. Ectoparasites can have a marked impact on already-declining woodrat populations across their range and should not be overlooked in future surveys.

A genome-wide association analysis reveals new pathogenic pathways in gout.

Gout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout). An additional 65 loci with signals in urate (from a GWAS of 630,117 individuals) but not gout were identified. A prioritization scheme identified candidate genes in the inflammatory process of gout, including genes involved in epigenetic remodeling, cell osmolarity and regulation of NOD-like receptor protein 3 (NLRP3) inflammasome activity. Mendelian randomization analysis provided evidence for a causal role of clonal hematopoiesis of indeterminate potential in gout. Our study identifies candidate genes and molecular processes in the inflammatory pathogenesis of gout suitable for follow-up studies.

Association of single-nucleotide polymorphisms in CCR6, TAGAP, and TNFAIP3 with rheumatoid arthritis in African Americans.

OBJECTIVE: We previously reported an analysis of single-nucleotide polymorphisms (SNPs) in 3 validated European rheumatoid arthritis (RA) susceptibility loci, TAGAP, TNFAIP3, and CCR6, in African American patients with RA. Unexpectedly, the disease-associated alleles were different in African Americans from those in Europeans. In an effort to better define their contribution, we performed additional SNP genotyping in these genes. METHODS: Seven SNPs were genotyped in 446 African American patients with RA and in 733 African American control subjects. Differences in minor allele frequency between the RA cases and controls were analyzed after controlling for the global proportion of European admixture, and pairwise linkage disequilibrium (LD) was estimated among the SNPs. RESULTS: Three SNPs were significantly associated with RA: the TNFAIP3 rs719149 A allele (OR 1.22 [95% confidence interval (95% CI) 1.03-1.44], P = 0.02), the TAGAP rs1738074 G allele (OR 0.75 [95% CI 0.63-0.89, P = 0.0012), and the TAGAP rs4709267 G allele (OR 0.74 [95% CI 0.60-0.91], P = 0.004). Pairwise LD between the TAGAP SNPs was low (r(2) = 0.034). The haplotype containing minor alleles for both TAGAP SNPs was uncommon (4.5%). After conditional analysis of each TAGAP SNP, its counterpart remained significantly associated with RA (rs1738074 for rs4709267 P = 0.00001 and rs4709267 for rs1738074 P = 0.00005), suggesting independent effects. CONCLUSION: SNPs in regulatory regions of TAGAP and an intronic SNP (TNFAIP3) are potential susceptibility loci in African Americans. Pairwise LD, haplotype analysis, and SNP conditioning analysis suggest that these 2 SNPs in TAGAP are independent susceptibility alleles. Additional fine-mapping of this gene and functional genomic studies of these SNPs should provide further insight into the role of these genes in RA.

Gene expression patterns in peripheral blood cells associated with radiographic severity in African Americans with early rheumatoid arthritis.

Gene expression profiling may be used to stratify patients by disease severity to test the hypothesis that variable disease outcome has a genetic component. In order to define unique expression signatures in African American rheumatoid arthritis (RA) patients with severe erosive disease, we undertook a gene expression study using samples of RNA from peripheral blood mononuclear cells (PBMCs). RNA from baseline PBMC samples of 96 African American RA patients with early RA (<2 years disease duration) was hybridized to cDNA probes of the Illumina Human HT-V3 expression array. Expression analyses were performed using the ca. 25,000 cDNA probes, and then expression levels were compared to the total number of erosions in radiographs of the hands and feet at baseline and 36 months. Using a false discovery rate cutoff of Q = 0.30, 1,138 genes at baseline and 680 genes at 36 months significantly correlated with total erosions. No evidence of a signal differentiating disease progression, or change in erosion scores between baseline and 36 months, was found. Further analyses demonstrated that the differential gene expression signature was localized to the patients with the most erosive disease (>10 erosions). Ingenuity Pathway Analysis demonstrated that genes with fold change greater than 1.5 implicated immune pathways such as CTLA signaling in cytotoxic T lymphocytes. These results demonstrate that CLEAR patients with early RA having the most severe erosive disease, as compared to more mild cases (<10 erosions), may be characterized by a set of differentially expressed genes that represent biological pathways with relevance to autoimmune disease.

Fall migration, oceanic movement, and site residency patterns of eastern red bats (Lasiurus borealis) on the mid-Atlantic Coast.

Along the mid-Atlantic coast of the United States, eastern red bats (Lasiurus borealis) are present during fall mating and migration, though little is currently known about most aspects of bat migration. To reveal migration patterns, and understand drivers of over-water flight, we captured and radio-tagged 115 eastern red bats using novel technology, and subsequently tracked and described their movements throughout the region. We compared over-water flight movements to randomly generated patterns using a use-availability framework, and subsequently used a generalized linear mixed effects model to assess the relationship of over-water flight to atmospheric variables. We used hidden Markov models to assess daily activity patterns and site residency. Most bats with long-distance movements traveled in a southwesterly direction, however path vectors were often oriented interior toward the continental landmass rather than along the coastline. We observed that some bats transited wide sections of the Chesapeake and Delaware bays, confirming their ability to travel across large water bodies. This over-water flight typically occurred in the early hours of the night and during favorable flying conditions. If flight over large water bodies is a proxy for over-ocean flight, then collision risk at offshore wind turbines - a major source of migratory bat fatalities - may be linked nightly to warm temperatures that occur early in the fall season. Risk, then, may be somewhat predictable and manageable with mitigation options linking wind-energy operation to weather conditions and seasonality.

Hypertension severity, apparent treatment resistant hypertension and hyperuricemia in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: Prior studies have identified an association between hypertension and hyperuricemia; however, there has been limited research on the association between hypertension severity and hyperuricemia. METHOD: We studied 997 Black and white adults with serum urate data from the reasons for geographic and racial differences in stroke (REGARDS) study. Hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg or self-reported use of antihypertensive medication. Apparent treatment-resistant hypertension (aTRH) was defined as a SBP ≥ 140 mmHg or DBP ≥ 90 mmHg with concurrent use of three classes of antihypertensive medications, or taking four or more classes of antihypertensive medication regardless of BP level. Controlled BP was defined as SBP <140 mmHg and DBP <90 mmHg. RESULTS: Overall 5.9% of participants had aTRH and 36.6% had hyperuricemia, defined as serum urate >7.0 mg/dl for men and >6.0 mg/dl for women. After full multivariable adjustment, the odds ratio (OR) for hyperuricemia associated with hypertension was 1.60 [95% confidence interval (95% CI): 1.06-2.40]. Compared to participants not taking antihypertensive medication, the ORs for hyperuricemia for participants taking one, two and three classes of antihypertensive medication without aTRH were 1.98 (95% CI: 1.23-3.20), 2.08 (95% CI: 1.25-3.43), 4.31 (95% CI: 2.07-8.97), respectively, and 3.96 (95% CI: 1.75-8.96) for aTRH. Compared to participants without hypertension, the odds ratios for hyperuricemia were 1.67 (95% CI: 1.08-2.58) and 1.46 (95% CI: 0.88-2.44) among those with hypertension with and without controlled BP, respectively. Diuretic use was associated with a higher odds of hyperuricemia. CONCLUSION: This study suggests that individuals taking more classes of antihypertensive medication may benefit from monitoring for hyperuricemia.

Long-term spring through fall capture data of Eptesicus fuscus in the eastern USA before and after white-nose syndrome.

Emerging infectious diseases threaten wildlife populations. Without well monitored wildlife systems, it is challenging to determine accurate population and ecosystem losses following disease emergence. North American temperate bats present a unique opportunity for studying the broad impacts of wildlife disease emergence, as their federal monitoring programs were prioritized in the USA throughout the 20th century and they are currently threatened by the invasive fungal pathogen, Pseudogymnoascus destructans (Pd), which causes white-nose syndrome. Here we provide a long-term dataset for capture records of Eptesicus fuscus (big brown bat) across the eastern USA, spanning 16 years before and 14 years after Pd invasion into North America. These data represent 30,496 E. fuscus captures across 3,567 unique sites. We encourage the use of this dataset for quantifying impacts of wildlife disease and other threats to wildlife (e.g., climate change) with the incorporation of other available data. We welcome additional data contributions for E. fuscus captures across North and Central America as well as the inclusion of other variables into the dataset that contribute to the quantification of wildlife health.

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. RESULTS: The PRS was associated with earlier age at gout onset in men (ß = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; ß = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; ß = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (ß = 0.07 [95% CI -2.32, 2.45] in European women; ß = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; ß -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (ß = -2.42 [95% CI -3.37, -1.46] and ß = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (ß = -1.79 [95% CI -4.74, 1.16]). CONCLUSION: Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.

Variable nursery pollinator importance and its effect on plant reproductive success.

Nursery pollination, in which insects use as hosts the very plants they pollinate, ranges from obligate mutualism to parasitism. In the non-obligate interaction between Greya moths and the host Lithophragma sp., the relative density of nursery pollinators and copollinators, which do not use plant tissues for larval development, is a key determinant of the interaction's outcome. Silene (Caryophyllaceae) nursery pollination by Hadena moths (Lepidoptera: Noctuidae), studied primarily in Europe, is considered antagonistic because copollinators comprise a substantial proportion of the pollinator community. However, there are few studies that ascertain the direction of the Silene-Hadena interaction by taking into account both pollinator service and seed predation. Here, we report a novel comprehensive evaluation of the direction of the interaction between North American Hadena ectypa on Silene stellata, by comparing the relative contributions of nursery and copollinators to S. stellata pollination and relate this to variation in fruit predation and reproductive success of S. stellata across multiple sites and years. Hadena ectypa pollinator importance (pollen deposited/visit/h) varied between years, resulting from variable visitation rate. Copollinator importance was higher than H. ectypa in 1 year and equivalent in another. In two of three sites, lowered H. ectypa activity was not correlated with a significant decrease in plant reproductive success, indicating a negative interaction. Although pollinator service by H. ectypa is substantial in this system, copollinators' service is at least as great, and when the cost of fruit predation is factored in, the net effect of the interaction is parasitism of host plants.