Facilitators for increasing dental attendance of people from vulnerable groups: a rapid review of evidence relevant to the UK.

Objective To rapidly review facilitators of access for vulnerable groups and to evaluate their effectiveness.Methods Data sources: MEDLINE via Ovid. Publications in English from 2000. DATA SELECTION: Research involving 'vulnerable groups' relevant to UK health systems, with a primary outcome of increasing attendance. DATA EXTRACTION: One author extracted and tabulated data. These were audited by a second author. DATA SYNTHESIS: A narrative synthesis was produced.Results Data from 31 studies were available for ten vulnerable groups: people with learning, physical or sensory disabilities (n = 8); people experiencing homelessness (n = 6); prisoners (n = 4); asylum-seekers and refugees (n = 3); people living in socioeconomically deprived areas (n = 3); people with severe mental health conditions (n = 2); vulnerable children (n = 2); dependent older people (n = 1); Gypsy, Roma or Traveller groups (n = 1); and people with drug dependency (n = 1). Many facilitators involved organisational reform and more integration of health, social and other services. Other facilitators included: modification of premises; team development and skill-mix use; and awareness of needs and flexible services to meet them. Few studies evaluated effectiveness.Conclusion Although facilitators for access for vulnerable groups have been proposed, there is little evidence to support or refute their effectiveness. Efforts are needed to promote access for vulnerable groups in the UK with evaluation plans embedded.

The oral health of adults attending dental practices in England in 2018: a report of a novel method and findings.

Introduction National surveys of the oral health of adults are conducted decennially. For reasons of feasibility and cost, these only provide accurate information at large geographical areas. To address this, a survey of adults attending dental practices in England was undertaken.Aim To describe and discuss the survey method and findings.Method A clinical examination and questionnaire survey was conducted in a sample of English dental practices.Results Questionnaires (n = 16,572) and clinical examinations (n = 14,270) were completed with patients from 1,173 dental practices. Poorer oral health disproportionately affected older adults and those from more socioeconomically deprived areas. Over one in three from more deprived areas had untreated caries compared with one in five in the less deprived (36.2% vs 19.9%) and impacts of oral problems were nearly three times higher in the more deprived areas (27.9% vs 11.0%). Of those receiving NHS care, 28.7% and 46.2% reported they would struggle/be unable to pay a Band 2 and Band 3 NHS patient charge, respectively.Conclusion It is feasible to undertake a survey of adults in dental practices but care must be taken generalising the findings to the general population and comparing them with other surveys undertaken using different methods.

Validation of an artificial intelligence solution for acute triage and rule-out normal of non-contrast CT head scans.

PURPOSE: Non-contrast CT head scans provide rapid and accurate diagnosis of acute head injury; however, increased utilisation of CT head scans makes it difficult to prioritise acutely unwell patients and places pressure on busy emergency departments (EDs). This study validates an AI algorithm to triage patients presenting with Intracranial Haemorrhage (ICH) or Acute Infarct whilst also identifying a subset of patients as Normal, with the potential to function as a rule-out test. METHODS: In total, 390 CT head scans were collected from 3 institutions in the UK, US and India. Ground-truth labels were assigned by 3 FRCR consultant radiologists. AI performance, as well as the performance of 3 independent radiologists, was measured against ground-truth labels. RESULTS: The algorithm showed AUC values of 0.988 (0.978-0.994), 0.933 (0.901-0.961) and 0.939 (0.919-0.958) for ICH, Acute Infarct and Normal, respectively. Sensitivity/specificity for ICH and Acute Infarct were 0.988/0.925 and 0.833/0.927, respectively, compared to 0.907/0.991 and 0.618/0.977 for radiologists. AI rule-out of Normal scans achieved 0.93% negative predictive value (NPV) for the removal of 54.3% of Normal cases, compared to 86.8% NPV for radiologists. CONCLUSION: We show our algorithm can provide effective triage of ICH and Acute Infarct to prioritise acutely unwell patients. AI can also benefit clinical accuracy, with the algorithm identifying 91.3% of radiologist false negatives for ICH and 69.1% for Acute Infarct. Rule-out of Normal scans has huge potential for workload management in busy EDs, in this case removing 27.4% of all scans with no acute findings missed.

Conformation of graphene folding around single-walled carbon nanotubes.

The low bending rigidity of graphene facilitates the formation of folds into the structure. This curvature change affects the reactivity and electron transport of the sheet. One novel extension of this is the intercalation of small molecules into these folds. We construct a model incorporating a single-walled carbon nanotube into a sheet of folded graphene. Variational calculus techniques are employed to determine the minimum energy structure and the resulting curves are shown to agree well with molecular dynamics study. Graphical Abstract Using calculus of variations, the elastic bending energy and van der Waals energy are minimised giving rise to Euler-Lagrange equation for which analytical solutions are derived to determine the optimal curved sturctures of graphene wrapped around carbon nanotubes . Overall agreement between the analytical solutions (with different values of bending rigidities) and results from molecular dynamics simulations (grey) is shown here for (6,6), (8,8) and (10,10) armchair nanotubes, respectively.

The Self-Reported Oral Health Status and Dental Attendance of Smokers and Non-Smokers in England.

Smoking has been identified as the second greatest risk factor for global death and disability and has impacts on the oral cavity from aesthetic changes to fatal diseases such as oral cancer. The paper presents a secondary analysis of the National Adult Dental Health Survey (2009). The analysis used descriptive statistics, bivariate analyses and logistic regression models to report the self-reported oral health status and dental attendance of smokers and non-smokers in England. Of the 9,657 participants, 21% reported they were currently smoking. When compared with smokers; non-smokers were more likely to report 'good oral health' (75% versus 57% respectively, p<0.05). Smokers were twice as likely to attend the dentist symptomatically (OR = 2.27, CI = 2.02-2.55) compared with non-smoker regardless the deprivation status. Smokers were more likely to attend symptomatically in the most deprived quintiles (OR = 1.99, CI = 1.57-2.52) and perceive they had poorer oral health (OR = 1.77, CI = 1.42-2.20). The present research is consistent with earlier sub-national research and should be considered when planning early diagnosis and management strategies for smoking-related conditions, considering the potential impact dental teams might have on smoking rates.

Genome-wide linkage on chromosome 10q26 for a dimensional scale of major depression.

Major depressive disorder (MDD) is a common and potentially life-threatening mood disorder. Identifying genetic markers for depression might provide reliable indicators of depression risk, which would, in turn, substantially improve detection, enabling earlier and more effective treatment. The aim of this study was to identify rare variants for depression, modeled as a continuous trait, using linkage and post-hoc association analysis. The sample comprised 1221 Mexican-American individuals from extended pedigrees. A single dimensional scale of MDD was derived using confirmatory factor analysis applied to all items from the Past Major Depressive Episode section of the Mini-International Neuropsychiatric Interview. Scores on this scale of depression were subjected to linkage analysis followed by QTL region-specific association analysis. Linkage analysis revealed a single genome-wide significant QTL (LOD=3.43) on 10q26.13, QTL-specific association analysis conducted in the entire sample revealed a suggestive variant within an intron of the gene LHPP (rs11245316, p=7.8×10(-04); LD-adjusted Bonferroni-corrected p=8.6×10(-05)). This region of the genome has previously been implicated in the etiology of MDD; the present study extends our understanding of the involvement of this region by highlighting a putative gene of interest (LHPP).

Dental auxiliaries for dental care traditionally provided by dentists.

BACKGROUND: Poor or inequitable access to oral health care is commonly reported in high-, middle- and low-income countries. Although the severity of these problems varies, a lack of supply of dentists and their uneven distribution are important factors. Delegating care to dental auxiliaries could ease this problem, extend services to where they are unavailable and liberate time for dentists to do more complex work. Before such an approach can be advocated, it is important to know the relative effectiveness of dental auxiliaries and dentists. OBJECTIVES: To assess the effectiveness, costs and cost effectiveness of dental auxiliaries in providing care traditionally provided by dentists. SEARCH METHODS: We searched the following electronic databases from their inception dates up to November 2013: the Cochrane Effective Practice and Organisation of Care (EPOC) Group's Specialised Register; Cochrane Oral Health Group's Specialised Register; the Cochrane Central Register of Controlled Trials (Issue 11, 2013); MEDLINE; EMBASE; CINAHL; Cochrane Database of Systematic Reviews; Database of Abstracts of Reviews of Effectiveness; five other databases and two trial registries. We also undertook a grey literature search and searched the reference list of included studies and contacted authors of relevant papers. SELECTION CRITERIA: We included randomised controlled trials (RCTs), non-randomised controlled clinical trials (NRCTs), interrupted time series (ITSs) and controlled before and after studies (CBAs) evaluating the effectiveness of dental auxiliaries compared with dentists in undertaking clinical tasks traditionally performed by a dentist. DATA COLLECTION AND ANALYSIS: Three review authors independently applied eligibility criteria, extracted data and assessed the risk of bias of each included study and two review authors assessed the quality of the evidence from the included studies, according to The Cochrane Collaboration's procedures. Since meta-analysis was not possible, we gave a narrative description of the results. MAIN RESULTS: We identified five studies (one cluster RCT, three RCTs and one NRCT), evaluating the effectiveness of dental auxiliaries compared with dentists in providing dental care traditionally provided by dentists, eligible for inclusion in this review. The included studies, which involved 13 dental auxiliaries, six dentists, and more than 1156 participants, evaluated two clinical tasks/techniques: placement of preventive resin fissure sealants and the atraumatic restorative technique (ART). Two studies were conducted in the US, and one each in Canada, Gambia and Singapore.Of the four studies evaluating effectiveness in placing preventive resin fissure sealants, three found no evidence of a difference in retention rates of those placed by dental auxiliaries and dentists over a range of follow-up periods (six to 24 months). One study found that fissure sealants placed by a dental auxiliary had lower retention rates than one placed by a dentist after 48 months (9.0% with auxiliary versus 29.1% with dentist). The same study reported that the net reduction after 48 months in the number teeth exhibiting caries (dental decay) was lower for teeth treated by the dental auxiliary than the dentist (3 with auxiliary versus 60 with dentist, P value < 0.001).One study showed no evidence of a difference in dental decay after treatment with fissure sealants between groups. The one study comparing the effectiveness of dental auxiliaries and dentists in performing ART reported no difference in survival rates of the restorations (fillings) after 12 months.All studies were at high risk of bias and the overall quality of the evidence was very low, as assessed using the GRADE approach. In addition, four of the included studies were more than 20 years old; the materials used and the techniques assessed were out of date. We found no eligible studies comparing the effectiveness of dental auxiliaries and dentists in the diagnosis of oral diseases and conditions, in delivering oral health education and other aspects of health promotion, or studies assessing participants' perspectives including the acceptability of care received. None of the included studies reported adverse effects. In addition, we found no studies comparing the costs and cost-effectiveness of dental auxiliaries and dentists, their impact on access and equity of access to care that met the pre-specified inclusion criteria. AUTHORS' CONCLUSIONS: We only identified five studies for inclusion in this review, all of which were at high risk of bias and four were published more than 20 years ago, highlighting the paucity of high-quality evaluations of the relative effectiveness, cost-effectiveness and safety of dental auxiliaries compared with dentists in performing clinical tasks. No firm conclusions could be drawn from the present review about the relative effectiveness of dental auxiliaries and dentists.

What influences the use of dental services by adults in the UK?

OBJECTIVES: Optimizing access to and utilization of dental services remains a major public health challenge. The aim of this study was to use Andersen's behavioural model to investigate the factors that influence utilization of dental services and predict oral health outcomes, and to identify how access could be improved. METHODS: Secondary analysis was conducted of data from a regional postal survey (n = 10 864) of adults in the UK. Items were chosen to reflect variables of Andersen's behavioural model including predisposing characteristics (deprivation), enabling resources (perceived difficulty accessing a dentist), need (perceived treatment need), health behaviours (reason for attendance and time since the last visit to the dentist) and oral health outcomes (oral health impacts (symptoms, functional limitation and social) and global oral health). Structural equation modelling was used to estimate the direct and indirect pathways between the variables within the model. RESULTS: When a combination of indirect and direct effects were taken into account, perceived difficulty accessing the dentist was associated with higher perceived treatment need (ß = 0.25, P < 0.01), increased oral health impacts (ß = -0.23, P < 0.01) and worse global oral health (ß = -0.21, P < 0.01). Overall, the variables included within this model explained 17.4% of the variance for dental attendance, 55.4% of the variance for the length of time since people had last visited the dentist, 21.7% of the variance for oral health impacts and 42.9% of the variance for people's global oral health. CONCLUSIONS: Perceived treatment need and difficulty accessing dental services were found to be key predictors of oral health outcomes. Further research is needed to develop and evaluate effective interventions to improve access to dental services.

Variants in the human potassium channel gene (KCNN3) are associated with migraine in a high risk genetic isolate.

The calcium-activated potassium ion channel gene (KCNN3) is located in the vicinity of the familial hemiplegic migraine type 2 locus on chromosome 1q21.3. This gene is expressed in the central nervous system and plays a role in neural excitability. Previous association studies have provided some, although not conclusive, evidence for involvement of this gene in migraine susceptibility. To elucidate KCNN3 involvement in migraine, we performed gene-wide SNP genotyping in a high-risk genetic isolate from Norfolk Island, a population descended from a small number of eighteenth century Isle of Man 'Bounty Mutineer' and Tahitian founders. Phenotype information was available for 377 individuals who are related through the single, well-defined Norfolk pedigree (96 were affected: 64 MA, 32 MO). A total of 85 SNPs spanning the KCNN3 gene were genotyped in a sub-sample of 285 related individuals (76 affected), all core members of the extensive Norfolk Island 'Bounty Mutineer' genealogy. All genotyping was performed using the Illumina BeadArray platform. The analysis was performed using the statistical program SOLAR v4.0.6 assuming an additive model of allelic effect adjusted for the effects of age and sex. Haplotype analysis was undertaken using the program HAPLOVIEW v4.0. A total of four intronic SNPs in the KCNN3 gene displayed significant association (P < 0.05) with migraine. Two SNPs, rs73532286 and rs6426929, separated by approximately 0.1 kb, displayed complete LD (r (2) = 1.00, D' = 1.00, D' 95% CI = 0.96-1.00). In all cases, the minor allele led to a decrease in migraine risk (beta coefficient = 0.286-0.315), suggesting that common gene variants confer an increased risk of migraine in the Norfolk pedigree. This effect may be explained by founder effect in this genetic isolate. This study provides evidence for association of variants in the KCNN3 ion channel gene with migraine susceptibility in the Norfolk genetic isolate with the rarer allelic variants conferring a possible protective role. This the first comprehensive analysis of this potential candidate gene in migraine and also the first study that has utilised the unique Norfolk Island large pedigree isolate to implicate a specific migraine gene. Studies of additional variants in KCNN3 in the Norfolk pedigree are now required (e.g. polyglutamine variants) and further analyses in other population data sets are required to clarify the association of the KCNN3 gene and migraine risk in the general outbred population.

The path to open-angle glaucoma gene discovery: endophenotypic status of intraocular pressure, cup-to-disc ratio, and central corneal thickness.

PURPOSE. Primary open-angle glaucoma (POAG) is a complex disease with a genetic architecture that can be simplified through the investigation of individual traits underlying disease risk. It has been well studied in twin models, and this study was undertaken to investigate the heritability of some of these key endophenotypes in extended pedigrees. METHODS. These data are derived from a large, multicenter study of extended, Caucasian POAG families from Australia and the United States. The study included 1181 people from 22 extended pedigrees. Variance components modeling was used to determine the heritabilities of maximum intraocular pressure (IOP), maximum vertical cup-to-disc ratio (VCDR), and mean central corneal thickness (CCT). Bivariate quantitative genetic analysis between these eye-related phenotypes and POAG itself was performed to determine whether any of these traits represent true endophenotypes. RESULTS. Heritability estimates for IOP, VCDR, and CCT (0.42, 0.66, and 0.72, respectively) were significant and show strong concordance with data in previous studies. Bivariate analysis revealed that both IOP (RhoG = 0.80; P = 9.6 x 10(-6)) and VCDR (RhoG = 0.76; P = 4.8 x 10(-10)) showed strong evidence of genetic correlation with POAG susceptibility. These two traits also correlated genetically with each other (RhoG = 0.45; P = 0.0012). Alternatively, CCT did not correlate genetically with risk of POAG. CONCLUSIONS. All the proposed POAG-related traits have genetic components. However, the significant genetic correlations observed between IOP, VCDR, and POAG itself suggest that they most likely represent true endophenotypes that could aid in the identification of genes underlying POAG susceptibility. CCT did not correlate genetically with disease and is unlikely to be a useful surrogate endophenotype for POAG.

The characterization of Abelson helper integration site-1 in skeletal muscle and its links to the metabolic syndrome.

The human Abelson helper integration site-1 (AHI1) gene is associated with both neurologic and hematologic disorders; however, it is also located in a chromosomal region linked to metabolic syndrome phenotypes and was identified as a type 2 diabetes mellitus susceptibility gene from a genomewide association study. To further define a possible role in type 2 diabetes mellitus development, AHI1 messenger RNA expression levels were investigated in a range of tissues and found to be highly expressed in skeletal muscle as well as displaying elevated levels in brain regions and gonad tissues. Further analysis in a rodent polygenic animal model of obesity and type 2 diabetes mellitus identified increased Ahi-1 messenger RNA levels in red gastrocnemius muscle from fasted impaired glucose-tolerant and diabetic rodents compared with healthy animals (P < .002). Moreover, elevated gene expression levels were confirmed in skeletal muscle from fasted obese and type 2 diabetes mellitus human subjects (P < .02). RNAi-mediated suppression of Ahi-1 resulted in increased glucose transport in rat L6 myotubes in both the basal and insulin-stimulated states (P < .01). Finally, single nucleotide polymorphism association studies identified 2 novel AHI1 genetic variants linked with fasting blood glucose levels in Mexican American subjects (P < .037). These findings indicate a novel role for AHI1 in skeletal muscle and identify additional genetic links with metabolic syndrome phenotypes suggesting an involvement of AHI1 in the maintenance of glucose homeostasis and type 2 diabetes mellitus progression.

Association of POAG risk factors and the Thr377Met MYOC mutation in an isolated Greek population.

PURPOSE: To characterize the MYOC genotype correlation with phenotypes in an isolated Greek population with a high incidence of glaucoma. METHODS: Five hundred thirty-one villagers were enrolled in the study. Participants underwent a comprehensive ophthalmic examination. All three exons of myocilin were bidirectionally sequenced. Power calculations and measured genotype analysis was conducted using the genetic variance analysis program, SOLAR version 4.2, to account for the relatedness between individuals. RESULTS: The participants, 376 of whom were linked in a single 11-generation pedigree, ranged in age from 10 to 95 years with a mean age of 49. Sixty-five individuals had POAG, and 27 of those carried the Thr377Met MYOC mutation. Both peak intraocular pressure and vertical cup-to dis- ratio were significantly associated with the MYOC Thr377Met variant (P = 9 x 10(-14) and P = 9 x 10(-8), respectively), whereas central corneal thickness showed no significant association (P < 0.7). CONCLUSIONS: This village had a high frequency of glaucoma, with 12% of the participants aged 10 to 95 years having the disease. In this cohort, the Thr377Met MYOC mutation was significantly associated with both high intraocular pressures and high vertical cup-to-disc ratios. No association was found with central corneal thickness.

Legacy of mutiny on the Bounty: founder effect and admixture on Norfolk Island.

The population of Norfolk Island, located off the eastern coast of Australia, possesses an unusual and fascinating history. Most present-day islanders are related to a small number of the 'Bounty' mutineer founders. These founders consisted of Caucasian males and Polynesian females and led to an admixed present-day population. By examining a single large pedigree of 5742 individuals, spanning >200 years, we analyzed the influence of admixture and founder effect on various cardiovascular disease (CVD)-related traits. On account of the relative isolation of the population, on average one-third of the genomes of present-day islanders (single large pedigree individuals) is derived from 17 initial founders. The proportion of Polynesian ancestry in the present-day individuals was found to significantly influence total triglycerides, body mass index, systolic blood pressure and diastolic blood pressure. For various cholesterol traits, the influence of ancestry was less marked but overall the direction of effect for all CVD-related traits was consistent with Polynesian ancestry conferring greater CVD risk. Marker-derived homozygosity was computed and agreed with measures of inbreeding derived from pedigree information. Founder effect (inbreeding and marker-derived homozygosity) significantly influenced height. In conclusion, both founder effect and extreme admixture have substantially influenced the genetic architecture of a variety of CVD-related traits in this population.

The modified dental anxiety scale: UK general public population norms in 2008 with further psychometrics and effects of age.

BACKGROUND: The Modified Dental Anxiety Scale (MDAS) is a brief, self-complete questionnaire consisting of five questions and summed together to produce a total score ranging from 5 to 25. It has reasonable psychometric properties, low instrumental effects and can be integrated into everyday dental practice as a clinical aid and screen for dental anxiety. The objectives were to (i) produce confirmatory evidence of reliability and validity for the MDAS, (ii) provide up-to-date UK representative norms for the general public to enable clinicians to compare their patients' scores, (iii) to determine the nature of the relationship between dental anxiety and age. METHODS: Telephone survey of a representative quota sample of 1000 UK adults (>18 years of age) conducted between 7-21 April, 2008. RESULTS: Attrition of potential participants was high in the recruitment process, although bias was minimal. Estimated proportion of participants with high dental anxiety (cut-off score = 19) was 11.6%. Dental anxiety was four times greater in the youngest age group (18-39 yrs) compared to older participants (60+ yrs), controlling for sex, social class and self-reported dental visiting behaviour confirming previous developed-world reports. CONCLUSION: The scale's psychometrics is supportive for the routine assessment of patient dental anxiety to compare against a number of major demographic groups categorised by age and sex. Dental anxiety was high in younger compared to older people.

Two quantitative trait loci influence whipworm (Trichuris trichiura) infection in a Nepalese population.

BACKGROUND: Whipworm (Trichuris trichiura) infection is a soil-transmitted helminth infection that affects >1 billion people. It is a serious public health problem in many developing countries and can result in deficits in growth and cognitive development. In a follow-up study of significant heritability for whipworm infection, we conducted the first genome scan for quantitative trait loci (QTL) influencing the heritability of susceptibility to this important parasitic disease. METHODS: Whipworm egg counts were determined for 1,253 members of the Jirel population of eastern Nepal. All individuals in the study sample belonged to a single pedigree including >26,000 pairs of relatives that are informative for genetic analysis. RESULTS: Linkage analysis of genome scan data generated for the pedigree provided unambiguous evidence for 2 QTL influencing susceptibility to whipworm infection, one located on chromosome 9 (logarithm of the odds ratio [LOD] score, 3.35; genomewide P = .0138) and the other located on chromosome 18 (LOD score, 3.29; genomewide P = .0159). There was also suggestive evidence that 2 loci located on chromosomes 12 and 13 influenced whipworm infection. CONCLUSION: The results of this first genome scan for T. trichiura egg counts provides new information on the determinants of genetic predisposition to whipworm infection.

Genome-wide linkage analyses of type 2 diabetes in Mexican Americans: the San Antonio Family Diabetes/Gallbladder Study.

The San Antonio Family Diabetes/Gallbladder Study was initiated to identify susceptibility genes for type 2 diabetes. Evidence was previously reported of linkage to diabetes on 10q with suggestive evidence on 3p and 9p in a genome-wide scan of 440 individuals from 27 pedigrees ascertained through a single diabetic proband. Subsequently, the study was expanded to include 906 individuals from 39 extended Mexican-American pedigrees, two additional examination cycles approximately 5.3 and 7.6 years after baseline, and genotypes for a new set of genome-wide markers. Therefore, we completed a second genome-wide linkage scan. Using information from a participant's most recent exam, the prevalence of diabetes in nonprobands was 21.8%. We performed genome-wide variance components-based genetic analysis on the discrete trait diabetes using a liability model and on the quantitative Martingale residual obtained from modeling age of diabetes diagnosis using Cox proportional hazard models. Controlling for age and age(2), our strongest evidence for linkage to the trait diabetes and the quantitative Martingale residual was on chromosome 3p at marker D3S2406 with multipoint empirical logarithm of odds scores of 1.87 and 3.76, respectively. In summary, we report evidence for linkage to diabetes on chromosome 3p in a region previously identified in at least three independent populations.

Phenotypic, genetic, and genome-wide structure in the metabolic syndrome.

BACKGROUND: Insulin resistance, obesity, dyslipidemia, and high blood pressure characterize the metabolic syndrome. In an effort to explore the utility of different multivariate methods of data reduction to better understand the genetic influences on the aggregation of metabolic syndrome phenotypes, we calculated phenotypic, genetic, and genome-wide LOD score correlation matrices using five traits (total cholesterol, high density lipoprotein cholesterol, triglycerides, systolic blood pressure, and body mass index) from the Framingham Heart Study data set prepared for the Genetic Analysis Workshop 13, clinic visits 10 and 1 for the original and offspring cohorts, respectively. We next applied factor analysis to summarize the relationship between these phenotypes. RESULTS: Factors generated from the genetic correlation matrix explained the most variation. Factors extracted using the other matrices followed a different pattern and suggest distinct effects. CONCLUSIONS: Given these results, different methods of multivariate data reduction may provide unique clues on the clustering of this complex syndrome.

HDL cholesterol in females in the Framingham Heart Study is linked to a region of chromosome 2q.

BACKGROUND: Despite strong evidence for a genetic component to variation in high-density lipoprotein cholesterol levels (HDL-C), specific polymorphisms associated with normal variation in HDL-C have not been identified. It is known, however, that HDL-C levels are influenced in complex ways by factors related to age and sex. In this paper, we examined the evidence for age- and sex-specific linkage of HDL-C in a longitudinal sample of participants from the Framingham Heart Study. To determine if aging could influence our ability to detect linkage, we explored the evidence for linkage of HDL-C at three time points, t1, t2, and t3, spaced approximately 8 years apart and corresponding respectively to visits 11, 15, and 20 for the original cohort and 1, 2, and 4 for the offspring and spouses. Additionally, to examine the effects of sex on linkage at each time point, we estimated the heritability and genetic correlation of HDL-C, performed linkage analysis of HDL-C, tested for genotype-by-sex interaction at a QTL, and performed linkage analysis of HDL-C in males and females separately. RESULTS AND CONCLUSION: In women, we found evidence for a QTL on chromosome 2q influencing HDL-C variation. Although the QTL could be detected in the combined sample of males and females at the first time point, the linkage was not significant at subsequent time points.