Population-based Reference Data Research Articles

National population-based reference data for the Hip Disability and Osteoarthritis Outcome Score (HOOS).

Interpretation of patient-reported outcome scores such as the Hip Disability and Osteoarthritis Outcome Score (HOOS) can be improved with use of reference values. The aim of the study was to establish population-based reference values for the HOOS' five subscales and its short-form HOOS-12. A representative sample of 9997 Danish citizens 18years and older were identified. The population record-based sample was based on seven predefined age groups and an equal sex distribution within each age group. A national secure electronic system was used to send the HOOS questionnaire and one supplementary question regarding previous hip complaints to all participants. 2277 participants completed the HOOS, 947 women (42%) and 1330 men (58%). The mean HOOS subscale scores were: pain 86.9 (95% CI 86.1-87.7), symptoms 83.7 (95% CI 82.9-84.5), ADL 88.2 (95% CI 87.5-89.0), sport and recreation function 83.1 (95% CI 82.0-84.1), QOL 82.7 (95% CI 81.8-83.6). The youngest age group reported better mean scores in four subscales compared to the oldest age group (pain 91.7 vs. 84.5, mean difference 7.2 95% CI 0.4-14.0), (ADL 94.6 points vs. 83.2, mean difference 11.4 95% CI 4.9-17.8), (sport and recreation function 91.5 points vs. 73.8 points, mean difference 17.7 95% CI 9.0-26.4), (QOL 88.9 points vs. 78.8, mean difference 10.1 points 95% CI 2.0-18.2). Participants with a self-reported hip complaint had worse HOOS scores across all subscales (mean difference range 22.1-34.6). Super obese patients (BMI > 40) had > 12.5 points worse scores across the five HOOS subscales. Results were similar for the HOOS-12. This study provides reference values for the HOOS and its short form HOOS-12. Results show that older patients and patients with a BMI over 40 have worse HOOS and HOOS-12 scores that may be of clinical importance in the interpretation of scores both when evaluating potential for improvement and post-treatment results.

Excess risk of SARS‐CoV‐2 infection among in‐person nonhealthcare workers in six states, September 2020–June 2021

While the occupational risk of severe acute respiratory syndromecoronavirus 2 (SARS-CoV-2) infection for healthcare personnel in the United States has been relatively well characterized, less information is available on the occupational risk for workers employed in other settings. Even fewer studies have attempted to compare risks across occupations and industries. Using differential proportionate distribution as an approximation, we evaluated excess risk of SARS-CoV-2 infection by occupation and industry among non-healthcare workers in six states. We analyzed data on occupation and industry of employment from a six-state callback survey of adult non-healthcare workers with confirmed SARS-CoV-2 infection and population-based reference data on employment patterns, adjusted for the effect of telework, from the U.S. Bureau of Labor Statistics. We estimated the differential proportionate distribution of SARS-CoV-2 infection by occupation and industry using the proportionate morbidity ratio (PMR). Among a sample of 1111 workers with confirmed SARS-CoV-2 infection, significantly higher-than-expected proportions of workers were employed in service occupations (PMR 1.3, 99% confidence interval [CI] 1.1-1.5) and in the transportation and utilities (PMR 1.4, 99% CI 1.1-1.8) and leisure and hospitality industries (PMR 1.5, 99% CI 1.2-1.9). We found evidence of significant differences in the proportionate distribution of SARS-CoV-2 infection by occupation and industry among respondents in a multistate, population-based survey, highlighting the excess risk of SARS-CoV-2 infection borne by some worker populations, particularly those whose jobs require frequent or prolonged close contact with other people.

Interpreting variants in genes affected by clonal hematopoiesis in population data.

Reference population databases like the Genome Aggregation Database (gnomAD) have improved our ability to interpret the human genome. Variant frequencies and frequency-derived tools (such as depletion scores) have become fundamental to variant interpretation and the assessment of variant-gene-disease relationships. Clonal hematopoiesis (CH) obstructs variant interpretation as somatic variants that provide proliferative advantage will affect variant frequencies, depletion scores, and downstream filtering. Further, default filtering of variants or genes associated with CH risks filtering bona fide germline variants as variants associated with CH can also cause Mendelian conditions. Here, we provide our insights on interpreting population variant data in genes affected by clonal hematopoiesis, as well as recommendations for careful review of 36 established CH genes associated with neurodevelopmental conditions.

Whole Exome Sequencing in South Africa: Stakeholder Views on Return of Individual Research Results and Incidental Findings.

The use of whole exome sequencing (WES) in medical research is increasing in South Africa (SA), raising important questions about whether and which individual genetic research results, particularly incidental findings, should be returned to patients. Whilst some commentaries and opinions related to the topic have been published in SA, there is no qualitative data on the views of professional stakeholders on this topic. Seventeen participants including clinicians, genomics researchers, and genetic counsellors (GCs) were recruited from the Western Cape in SA. Semi-structured interviews were conducted, and the transcripts analysed using the framework approach for data analysis. Current roadblocks for the clinical adoption of WES in SA include a lack of standardised guidelines; complexities relating to variant interpretation due to lack of functional studies and underrepresentation of people of African ancestry in the reference genome, population and variant databases; lack of resources and skilled personnel for variant confirmation and follow-up. Suggestions to overcome these barriers include obtaining funding and buy-in from the private and public sectors and medical insurance companies; the generation of a locally relevant reference genome; training of health professionals in the field of genomics and bioinformatics; and multidisciplinary collaboration. Participants emphasised the importance of upscaling the accessibility to and training of GCs, as well as upskilling of clinicians and genetic nurses for return of genetic data in collaboration with GCs and medical geneticists. Future research could focus on exploring the development of stakeholder partnerships for increased access to trained specialists as well as community engagement and education, alongside the development of guidelines for result disclosure.

Variant interpretation using population databases: Lessons from gnomAD.

Reference population databases are an essential tool in variant and gene interpretation. Their use guides the identification of pathogenic variants amidst the sea of benign variation present in every human genome, and supports the discovery of new disease–gene relationships. The Genome Aggregation Database (gnomAD) is currently the largest and most widely used publicly available collection of population variation from harmonized sequencing data. The data is available through the online gnomAD browser (https://gnomad.broadinstitute.org/) that enables rapid and intuitive variant analysis. This review provides guidance on the content of the gnomAD browser, and its usage for variant and gene interpretation. We introduce key features including allele frequency, per‐base expression levels, constraint scores, and variant co‐occurrence, alongside guidance on how to use these in analysis, with a focus on the interpretation of candidate variants and novel genes in rare disease.

Driving mosaicism: somatic variants in reference population databases and effect on variant interpretation in rare genetic disease

BackgroundGenetic variation databases provide invaluable information on the presence and frequency of genetic variants in the ‘untargeted’ human population, aggregated with the primary goal to facilitate the interpretation of clinically important variants. The presence of somatic variants in such databases can affect variant assessment in undiagnosed rare disease (RD) patients. Previously, the impact of somatic mosaicism was only considered in relation to two Mendelian disease-associated genes. Here, we expand the analyses to identify additional mosaicism-prone genes in blood-derived reference population databases.ResultsTo identify additional mosaicism-prone genes relevant to RDs, we focused on known/previously established ClinVar pathogenic and likely pathogenic single-nucleotide variants, residing in genes associated with early onset, severe autosomal dominant diseases. We asked whether any of these variants are present in a higher-than-expected frequency in the reference population databases and whether there is evidence of somatic origin (i.e., allelic imbalance) rather than germline heterozygosity (~ half of the reads supporting alternative allele). The mosaicism-prone genes identified were further categorized according to the processes they are involved in. Beyond the previously reported ASXL1 and DNMT3A, we identified 7 additional autosomal dominant RD-associated genes with known pathogenic single-nucleotide variants present in the reference population databases and good evidence of allelic imbalance: BRAF, CBL, FGFR3, IDH2, KRAS, PTPN11 and SETBP1. From this group of 9 genes, the majority (n = 7) was important for hematopoiesis. In addition, 4 of these genes were involved in cell proliferation. Further assessment of the known 156 hematopoietic genes led to identification of 48 genes (21 not yet associated with RDs) with at least some evidence of mosaicism detectable in reference population databases.ConclusionsThese results stress the importance of considering genes involved in hematopoiesis and cell proliferation when interpreting the presence and frequency of genetic variants in blood-derived reference population databases, both public and private. This is especially important when considering new variants of uncertain significance in known hematopoietic/cell proliferation RD genes and future novel gene–disease associations involving this class of genes.

Severe multisystem pathology, metabolic acidosis, mitochondrial dysfunction, and early death associated with an X-linked AIFM1 variant.

Variants in the X-linked gene AIFM1 (apoptosis-inducing factor mitochondria-associated 1) are associated with a highly variable clinical presentation that encompasses motor neuropathy, ataxia, encephalopathies, deafness, and cognitive impairment. AIFM1 encodes a mitochondrial flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide (NADH) oxidoreductase, with roles in the regulation of respiratory complex assembly and function, production of reactive oxygen species, and the coordination of a caspase-independent type of apoptosis known as parthanatos. In this report, we describe a missense AIFM1 variant (absent in reference population databases; c.506C > T, p.Pro169Leu) identified in the proband and sibling of a family with three affected males. The proband, his brother, and their maternal uncle all exhibited severe multisystem pathology, metabolic acidosis, and early demise. Metabolic testing on the proband revealed normal activity of the pyruvate dehydrogenase complex in skin fibroblasts. Absent or partial deficiency of cytochrome c oxidase was found in muscle fibers, however, supporting a Complex IV mitochondrial deficiency. Functional studies carried out on fibroblasts from the proband demonstrated reduced steady state levels of the AIFM1 protein, decreased Complex I subunit abundance, elevated sensitivity to the apoptosis inducer staurosporine, and increased nuclear condensation when grown in galactose-containing media. The reduced abundance of AIFM1 in the patient cells could not be stabilized with riboflavin or protease inhibitor treatment. Together, these findings suggest that the normal function of the AIFM1 gene product within mitochondria, and its response to apoptotic stimuli, are impaired by this variant, likely accounting for the severity of the phenotype seen in these patients. These findings also imply tissue-specific effects of this variant on different mitochondrial complexes. This study expands the genetic and phenotypic spectrum associated with AIFM1 variants, with the combination of exome sequencing and functional studies allowing a diagnosis to finally be confirmed for this family.

Norwegian reference data on the Fatigue Questionnaire and the Patient Health Questionnaire-9 and their interrelationship

BackgroundPopulation-based reference data on frequently used questionnaires are important for comparative purposes. Due to changes in health and lifestyles, such data should be updated every other decade. The objectives of this study were to establish Norwegian population-based reference data on the Fatigue Questionnaire (FQ) and the Patient Health Questionnaire-9 (PHQ-9) on depression, to compare the FQ-scores with our previous reference data from 1996, and to explore the relationship between the scores on these two instruments.MethodsIn 2015, a representative sample of 6,012 Norwegians aged 18–80 years was mailed a questionnaire including the FQ and the PHQ-9, and 36% responded. Complete FQ-scores were delivered by 2,041 subjects, and complete PHQ-9 scores by 2,086 subjects. The scores are displayed according to sex and 10-year age groups.ResultsFew 2015 mean scores of mental, physical, and total fatigue differed significantly from those of 1996, and the same was found for the prevalence rates of chronic fatigue. The exception was a significantly lower prevalence in 2015 of mean fatigue scores and prevalence of chronic fatigue in females ≥ 60 years. The prevalence of major depressive episode (MDE) based on the PHQ-9 sum score cut-off ≥ 10 was 5.9% for males and 9.8% for females, and 2.5% and 3.8% using a DSM-based algorithm with at least five endorsed criteria including either anhedonia or depressed mood. The correlation between the FQ and the PHQ-9 was 0.59, implying 36% shared variance.ConclusionsThis study showed considerable interrelationship between the FQ and the PHQ-9 constructs. The reference data show that scores on the FQ have only improved significantly in persons aged 60 or more years between 1996 and 2015. Our prevalence findings of MDE based on the PHQ-9 are in accordance with the findings from other countries. The FQ and the PHQ-9 should be used together in epidemiological and clinical studies.

The Brazilian Initiative on Precision Medicine (BIPMed): fostering genomic data-sharing of underrepresented populations

The development of precision medicine strategies requires prior knowledge of the genetic background of the target population. However, despite the availability of data from admixed Americans within large reference population databases, we cannot use these data as a surrogate for that of the Brazilian population. This lack of transferability is mainly due to differences between ancestry proportions of Brazilian and other admixed American populations. To address the issue, a coalition of research centres created the Brazilian Initiative on Precision Medicine (BIPMed). In this study, we aim to characterise two datasets obtained from 358 individuals from the BIPMed using two different platforms: whole-exome sequencing (WES) and a single nucleotide polymorphism (SNP) array. We estimated allele frequencies and variant pathogenicity values from the two datasets and compared our results using the BIPMed dataset with other public databases. Here, we show that the BIPMed WES dataset contains variants not included in dbSNP, including 6480 variants that have alternative allele frequencies (AAFs) >1%. Furthermore, after merging BIPMed WES and SNP array data, we identified 809,589 variants (47.5%) not present within the 1000 Genomes dataset. Our results demonstrate that, through the incorporation of Brazilian individuals into public genomic databases, BIPMed not only was able to provide valuable knowledge needed for the implementation of precision medicine but may also enhance our understanding of human genome variability and the relationship between genetic variation and disease predisposition.

Assessing the effects of accent-mismatched reference population databases on the performance of an automatic speaker recognition system

Automatic Speaker Recognition (ASR) systems are designed to provide the user with statistics relating to the similarity of two or more speech samples and to the typicality of those shared features in the wider population. When an ASR system is used as part of a forensic investigation, the user must decide what counts as the appropriate ‘wider population’ and select a reference database accordingly. While it has generally been held that the voices populating the reference database should be similar in accent to that of the samples under consideration, the degree to which the accents should correspond has until now not been investigated empirically. We report in this article on a study in which the composition of the reference database was systematically varied in terms of accent, using corpora of samples of Standard Southern British English and of three subvarieties spoken in North-East England (Newcastle, Sunderland, Middlesbrough).

Ethnic fragmentation and degree of urbanization strongly affect the discrimination power of Y-STR haplotypes in central Sahel

Y chromosome short tandem repeats (Y-STRs) are commonly used to identify male lineages for investigative and judicial purposes and could represent the only source of male-specific genetic information from unbalanced female-male mixtures. The Yfiler Plus multiplex, which includes twenty conventional and seven rapidly-mutating Y-STRs, represents the most discriminating patrilineal system commercially available to date. Over the past five years, this multiplex has been used to analyze several Eurasian populations, with a reported discrimination capacity (DC) approaching or corresponding to the highest possible value. However, despite the inclusion of rapidly mutating Y-STRs, extensive haplotype sharing was still reported for some African populations due to a number of different factors affecting the effective population size.In the present study, we analyzed 27 Y-STRs included in the Yfiler Plus multiplex and 82 Y-SNPs in central Sahel (northern Cameroon and western Chad), an African region characterized by a strong ethnic fragmentation and linguistic diversity. We evaluated the effects of population sub-structuring on genetic diversity by stratifying a sample composed of 431 males according to their ethnicity (44 different ethnic groups) and urbanization degree (four villages and four towns).Overall, we observed a low discrimination capacity (DC = 0.90), with 71 subjects (16.5 %) sharing 27 Y-STR haplotypes. Haplotype sharing was essentially limited to subjects with the same binary haplogroup, coming from the same location and belonging to the same ethnic group. Haplotype sharing was much higher in rural areas (average DC = 0.83) than urban settlements (average DC = 0.96) with a significant correlation between DC and census size (r = 0.89; p = 0.003). Notably, we found that genetic differentiation between villages from the same country (ΦST = 0.14) largely exceeded that found among countries (ΦST = 0.02). These findings have important implications for the choice of the appropriate reference population database to evaluate the statistical relevance of forensic Y-haplotype matches.

Sex- and Site-Specific Reference Data for Bone Microarchitecture in Adults Measured Using Second-Generation HR-pQCT.

There are currently no population-based reference data sets available for volumetric bone mineral density and microarchitecture parameters measured using the second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT), yet the technology is rapidly becoming a standard for studies of bone microarchitecture. Although cross-calibrated data sets from the first-generation HR-pQCT have been reported, they are not suitable for second-generation bone microarchitecture properties because of fundamental differences between scanner generations. This study provides site- and sex-specific centile curves across the adult life span for second-generation HR-pQCT properties. A total of 1236 adult participants (768 female and 468 male) from the Calgary area between the ages of 18 and 90 years were scanned at the distal tibia and radius using the second-generation HR-pQCT. Bone densities, microarchitectural properties, and failure load estimated using finite element analysis were determined using standard in vivo protocol. Site- and sex-specific centile curves were generated using the generalized additive models for location, scale, and shape (GAMLSS) method. These data provide reference curves appropriate for predominantly white male and female adults, which can be used as a tool to assess patient- or cohort-specific bone health. © 2020 American Society for Bone and Mineral Research.

Assessing the forensic efficiency of the GlobalFiler STR loci among the genetically isolated Chechen subpopulation in Jordan

Short tandem repeats (STRs) are a widely utilized tool in forensic applications, the latter of which range from human identification and paternity testing to population analysis. The GlobalFiler STR loci, which includes 21 autosomal STRS, were analyzed in the Chechen subpopulation of Jordan. Whole blood samples were withdrawn from 159 Jordanian Chechen individuals, and genomic DNA was extracted from each sample. The GlobalFiler™ kit PCR Amplification Kit amplified and analyzed the STR loci on the 3130xl Genetic Analyzer using GeneMapper ID-X software. The combined match probability for the 21 autosomal STR loci was calculated to be 1.06 × 10−24, a number that is highly discriminatory and informative. The SE33 (0.983) and TPOX (0.806) loci exhibited the highest and lowest powers of discrimination, respectively. Conclusively, the current study indicates that the GlobalFiler loci have a high utility in the Jordanian Chechen population, possibly paving the way for the future establishment of a reference population database in Jordan.

Mitochondrial DNA in human identification: a review.

Mitochondrial DNA (mtDNA) presents several characteristics useful for forensic studies, especially related to the lack of recombination, to a high copy number, and to matrilineal inheritance. mtDNA typing based on sequences of the control region or full genomic sequences analysis is used to analyze a variety of forensic samples such as old bones, teeth and hair, as well as other biological samples where the DNA content is low. Evaluation and reporting of the results requires careful consideration of biological issues as well as other issues such as nomenclature and reference population databases. In this work we review mitochondrial DNA profiling methods used for human identification and present their use in the main cases of humanidentification focusing on the most relevant issues for forensics.

TGF-β1 downregulation in the hypothalamus of obese mice through acute exercise.

Obesity and aging lead to abnormal transforming growth factor-β1 (TGF-β1) signaling in the hypothalamus, triggering the imbalance on glucose metabolism and energy homeostasis. Here, we determine the effect of acute exercise on TGF-β1 expression in the hypothalamus of two models of obesity in mice. The bioinformatics analysis was performed to evaluate the correlation between hypothalamic Tgf-β1 messenger RNA (mRNA) and genes related to thermogenesis in the brown adipose tissue (BAT) by using a large panel of isogenic BXD mice. Thereafter, leptin-deficient (ob/ob) mice and obese C57BL/6 mice fed on a high-fat diet (HFD) were submitted to the acute exercise protocol. Transcriptomic analysis by using BXD mouse reference population database revealed that hypothalamic Tgf-β1 mRNA is negatively correlated with genes related to thermogenesis in brown adipose tissue of BXD mice, such as peroxisome proliferator-activated receptor gamma coactivator and is positively correlated with respiratory exchange ratio. In agreement with these results, leptin-deficient (ob/ob) and HFD-fed mice displayed high levels of Tgf-β1 mRNA in the hypothalamus and reduction of Pgc1α mRNA in BAT. Interestingly, an acute exercise session reduced TGF-β1 expression in the hypothalamus, increased Pgc1α mRNA in the BAT and reduced food consumption in obese mice. Our results demonstrated that acute physical exercise suppressed hypothalamic TGF-β1 expression, increasing Pgc1α mRNA in BAT in obese mice.

Relevance of Titin Missense and Non-Frameshifting Insertions/Deletions Variants in Dilated Cardiomyopathy

Recent advancements in next generation sequencing (NGS) technology have led to the identification of the giant sarcomere gene, titin (TTN), as a major human disease gene. Truncating variants of TTN (TTNtv) especially in the A-band region account for 20% of dilated cardiomyopathy (DCM) cases. Much attention has been focused on assessment and interpretation of TTNtv in human disease; however, missense and non-frameshifting insertions/deletions (NFS-INDELs) are difficult to assess and interpret in clinical diagnostic workflow. Targeted sequencing covering all exons of TTN was performed on a cohort of 530 primary DCM patients from three cardiogenetic centres across Europe. Using stringent bioinformatic filtering, twenty-nine and two rare TTN missense and NFS-INDELs variants predicted deleterious were identified in 6.98% and 0.38% of DCM patients, respectively. However, when compared with those identified in the largest available reference population database, no significant enrichment of such variants was identified in DCM patients. Moreover, DCM patients and reference individuals had comparable frequencies of splice-region missense variants with predicted splicing alteration. DCM patients and reference populations had comparable frequencies of rare predicted deleterious TTN missense variants including splice-region missense variants suggesting that these variants are not independently causative for DCM. Hence, these variants should be classified as likely benign in the clinical diagnostic workflow, although a modifier effect cannot be excluded at this stage.

Hip complaints differ across age and sex: a population-based reference data for the Hip disability and Osteoarthritis Outcome Score (HOOS)

BackgroundThe Hip disability and Osteoarthritis Outcome Score (HOOS) is a self-administered hip-specific questionnaire intended to evaluate symptoms and functional limitations, and it is commonly used to evaluate interventions in individuals with hip dysfunction or hip osteoarthritis. The HOOS consists of 43 questions in five subscales: Pain, Symptoms, Function in daily living, Function in sport and recreation and Hip-Related Quality of Life. This study aimed to establish population-based reference values for the HOOS and to describe the variation of hip-related symptoms in an adult population.MethodsThe HOOS questionnaire was mailed to 840 individuals aged 18–84 years randomly retrieved from a national population record for the Skåne region of Southern Sweden.ResultsThe overall response rate was 67%. Older women and men consistently reported more hip-related complaints than those younger. There were significant differences between the oldest and the youngest age groups in all five subscales in women and men.ConclusionsHip-related pain, symptoms, activity of daily life and quality of life varied with age and sex in this population-based cohort. Our findings show the importance of using age- and sex-matched reference values for evaluation of outcomes after interventions due to hip-related problems.

Effect of DNA Profile Size, Reference Population Database, and Parents Availability on Parentage Testing in Consanguineous and Endogamous Populations: The Lebanese Case

Effect of DNA Profile Size, Reference Population Database, and Parents Availability on Parentage Testing in Consanguineous and Endogamous Populations: The Lebanese Case

The National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) \u2013 reference data from the German population-based Gutenberg Health Study (GHS)

BackgroundTo estimate the burden of diseases, it is important to consider patient-reported outcomes including Quality of Life (QoL). The aim of this study is to provide population-based reference data for the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25), stratified by sex and age.MethodsThe Gutenberg Health Study (GHS) is a population-based, prospective, observational cohort study in Germany, including 15,010 participants aged between 35 and 74. The baseline examination was conducted between 2007 and 2012. To overcome known shortcomings of the NEI VFQ-25, we calculated the previously proposed visual functioning scale and the socio-emotional scale based on Rasch-transformed person-level data. We present mean values, standard deviations and percentiles for age decades stratified by sex. We used a linear regression model to assess the influence of age, sex, socioeconomic status, distance-corrected visual acuity (better-seeing eye) and the absolute difference in distance-corrected visual acuity of both eyes on vision-related QoL.ResultsNEI VFQ-25 data are available from 12,231 participants (82%). Both the long-form visual functioning scale (LFVFS) and the long-form socio-emotional scale (LFSES) showed a clear age dependency, with an average LFVFS score of 92.8 for men and 90.5 for women in the youngest age group and 85.7 and 83.4 in the oldest age group, and a LFSES score of 98.3 for men and 98.1 in women in the youngest and 94.7 and 94.5 in the oldest decade. The largest difference was observed between the youngest age group (35–44 years) and the 45–54 years group. Men tended to have slightly higher scores than women. In the multivariable linear regression analysis, age (per 5 years −0.42), female sex (−1.57), worse distance-corrected visual acuity of the better eye (per 0.1 increase in logMAR −2.92) and the difference between both eyes (per 0.1 increase in logMAR −0.87) were associated with a reduced LFVFS score (all p < 0.001). For the LFSES score, we showed that the influence of sex was minor, and that age (per 5 years −0.22), visual acuity of the better eye (−1.65), and the difference between both eyes (−0.56) were associated with a lower score (all p < 0.001).ConclusionsWe report age- and sex-specific reference data from a large population-based study of mainly Caucasian ethnicity of two unidimensional scores based on Rasch-transformed NEI VFQ-25 data. Vision-related QoL is lower in older and in female individuals. Our results support the association of vision-related QoL not only with the distance-corrected visual acuity of the better eye but also with the difference in visual acuity between each eye. Our findings could be used as a reference for comparison in future studies addressing the influence of eye diseases on vision-related QoL.

Genetic differentiation of spring-spawning and fall-spawning male Atlantic sturgeon in the James River, Virginia.

Atlantic sturgeon (Acipenser oxyrinchus oxyrinchus, Acipenseridae) populations are currently at severely depleted levels due to historic overfishing, habitat loss, and pollution. The importance of biologically correct stock structure for effective conservation and management efforts is well known. Recent improvements in our understanding of Atlantic sturgeon migrations, movement, and the occurrence of putative dual spawning groups leads to questions regarding the true stock structure of this endangered species. In the James River, VA specifically, captures of spawning Atlantic sturgeon and accompanying telemetry data suggest there are two discrete spawning groups of Atlantic sturgeon. The two putative spawning groups were genetically evaluated using a powerful microsatellite marker suite to determine if they are genetically distinct. Specifically, this study evaluates the genetic structure, characterizes the genetic diversity, estimates effective population size, and measures inbreeding of Atlantic sturgeon in the James River. The results indicate that fall and spring spawning James River Atlantic sturgeon groups are genetically distinct (overall FST = 0.048, F’ST = 0.181) with little admixture between the groups. The observed levels of genetic diversity and effective population sizes along with the lack of detected inbreeding all indicated that the James River has two genetically healthy populations of Atlantic sturgeon. The study also demonstrates that samples from adult Atlantic sturgeon, with proper sample selection criteria, can be informative when creating reference population databases. The presence of two genetically-distinct spawning groups of Atlantic sturgeon within the James River raises concerns about the current genetic assignment used by managers. Other nearby rivers may also have dual spawning groups that either are not accounted for or are pooled in reference databases. Our results represent the second documentation of genetically distinct dual spawning groups of Atlantic sturgeon in river systems along the U.S. Atlantic coast, suggesting that current reference population database should be updated to incorporate both new samples and our increased understanding of Atlantic sturgeon life history.