Sprint,agility, strength and endurance capacity in wheelchair basketball players

The aims of the present study were, firstly, to determine the reliability and reproducibility of an agility T-test and Yo-Yo 10 m recovery test; and secondly, to analyse the physical characteristics measured by sprint, agility, strength and endurance field tests in wheelchair basketball (WB) players. 16 WB players (33.06 ± 7.36 years, 71.89 ± 21.71 kg and sitting body height 86.07 ± 6.82 cm) belonging to the national WB league participated in this study. Wheelchair sprint (5 and 20 m without ball, and 5 and 20 m with ball) agility (T-test and pick-up test) strength (handgrip and maximal pass) and endurance (Yo-Yo 10 m recovery test) were performed. T-test and Yo-Yo 10 m recovery test showed good reproducibility values (intraclass correlation coefficient, ICC = 0.74-0.94). The WB players’ results in 5 and 20 m sprints without a ball were 1.87 ± 0.21 s and 5.70 ± 0.43 s and with a ball 2.10 ± 0.30 s and 6.59 ± 0.61 s, being better than those reported in the literature. Regarding the pick-up test results (16.05 ± 0.52 s) and maximal pass (8.39 ± 1.77 m), players showed worse values than those obtained in elite players. The main contribution of the present study is the characterization of the physical performance profile of WB players using a field test battery. Furthermore, we demonstrated that the agility T-test and the aerobic Yo-Yo 10 m recovery test are reliable; consequently they may be appropriate instruments for measuring physical fitness in WB.     

Evaluation of the Bladder Stimulation Technique to Collect Midstream Urine in Infants in a Pediatric Emergency Department

Objective

Midstream clean-catch urine is an accepted method to diagnose urinary tract infection but is impracticable in infants before potty training. We tested the bladder stimulation technique to obtain a clean-catch urine sample in infants.

Materials and methods

We included 142 infants under walking age who required a urine sample in a cross- sectional study carried out during a 3-months period, from September to November 2014, in the emergency department of the University Children’s Hospital of Nice (France). A technique based on bladder stimulation and lumbar stimulation maneuvers, with at least two attempts, was tested by four trained physicians. The success rate and time to obtain urine sample within 3 minutes were evaluated. Discomfort (EVENDOL score ≥4/15) was measured. We estimated the risk factors in the failure of the technique. Chi-square test or Fisher’s exact test were used to compare frequencies. T-test and Wilcoxon test were used to compare quantitative data according to the normality of the distribution. Risk factors for failure of the technique were evaluated using a multivariate logistic regression model.

Results

We obtained midstream clean-catch urine in 55.6% of infants with a median time of 52.0 s (10.0; 110.0). The success rate decreased with age from 88.9% (newborn) to 28.6% (>1 y) (p = 0.0001) and with weight, from 85.7% (<4kg) to 28.6% (>10kg) (p = 0.0004). The success rate was 60.8% for infants without discomfort (p<0.0001). Heavy weight and discomfort were associated with failure, with adjusted ORs of 1.47 [1.04–2.31] and 6.65 [2.85–15.54], respectively.

Conclusion

Bladder stimulation seems to be efficient in obtaining midstream urine with a moderate success rate in our study sample. This could be an alternative technique for infants before potty training but further randomized multicenter studies are needed to validate this procedure.     

School Performance: A Matter of Health or Socio-Economic Background? Findings from the PIAMA Birth Cohort Study

Background

Performance in primary school is a determinant of children’s educational attainment and their socio-economic position and health inequalities in adulthood. We examined the relationship between five common childhood health conditions (asthma symptoms, eczema, general health, frequent respiratory infections, and overweight), health related school absence and family socio-economic status on children’s school performance.

Methods

We used data from 1,865 children in the Dutch PIAMA birth cohort study. School performance was measured as the teacher’s assessment of a suitable secondary school level for the child, and the child’s score on a standardized achievement test (Cito Test). Both school performance indicators were standardised using Z-scores. Childhood health was indicated by eczema, asthma symptoms, general health, frequent respiratory infections, overweight, and health related school absence. Children’s health conditions were reported repeatedly between the age of one to eleven. School absenteeism was reported at age eleven. Highest attained educational level of the mother and father indicated family socio-economic status. We used linear regression models with heteroskedasticity-robust standard errors for our analyses with adjustment for sex of the child.

Results

The health indicators used in our study were not associated with children’s school performance, independently from parental educational level, with the exception of asthma symptoms (-0.03 z-score / -0.04 z-score with Cito Test score after adjusting for respectively maternal and paternal education) and missing more than 5 schooldays due to illness (-0.18 z-score with Cito Test score and -0.17 z-score with school level assessment after adjustment for paternal education). The effect estimates for these health indicators were much smaller though than the effect estimates for parental education, which was strongly associated with children’s school performance.

Conclusion

Children’s school performance was affected only slightly by a number of common childhood health problems, but was strongly associated with parental education.     

The Impact of Diabetic Neuropathy on Balance and on the Risk of Falls in Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Study

IntroductionDiabetic neuropathy (DN) is a prevalent complication of Type 2 Diabetes Mellitus (T2DM) with a major impact on the health of the affected patient. We hypothesized that mediated by the dysfunctionalities associated with DN’s three major components: sensitive (lack of motion associated sensory), motor (impairments in movement coordination) and autonomic (the presence of postural hypotension), the presence of DN may impair the balance in the affected patients. Our study’s main aim is to evaluate the possible association between the presence and severity of DN and both the balance impairment and the risk of falls in patients with T2DM.ResultsThe presence of DN was associated with significant decreases in the BBS score (40.5 vs. 43.7 points; p<0.001) and SLS time (9.3 vs. 10.3 seconds; p = 0.003) respectively increases in TUG time (8.9 vs. 7.6 seconds; p = 0.002) and FES-I score (38 vs. 33 points; p = 0.034). The MNSI score was reverse and significantly correlated with both BBS score (Spearman’s r = -0.479; p<0.001) and SLS time (Spearman’s r = -0.169; p = 0.017). In the multivariate regression model, we observed that patient’s age, DN severity and depression’s symptoms acted as independent, significant predictors for the risk of falls in patients with T2DM.ConclusionsThe presence of DN in patients with DM is associated with impaired balance and with a consecutively increase in the risk of falls.     

Kinetics of MDR Transport in Tumor-Initiating Cells

Multidrug resistance (MDR) driven by ABC (ATP binding cassette) membrane transporters is one of the major causes of treatment failure in human malignancy. MDR capacity is thought to be unevenly distributed among tumor cells, with higher capacity residing in tumor-initiating cells (TIC) (though opposite finding are occasionally reported). Functional evidence for enhanced MDR of TICs was previously provided using a “side population” assay. This assay estimates MDR capacity by a single parameter - cell’s ability to retain fluorescent MDR substrate, so that cells with high MDR capacity (“side population”) demonstrate low substrate retention. In the present work MDR in TICs was investigated in greater detail using a kinetic approach, which monitors MDR efflux from single cells. Analysis of kinetic traces obtained allowed for the estimation of both the velocity (V _max) and affinity (K _M) of MDR transport in single cells. In this way it was shown that activation of MDR in TICs occurs in two ways: through the increase of V _max in one fraction of cells, and through decrease of K _M in another fraction. In addition, kinetic data showed that heterogeneity of MDR parameters in TICs significantly exceeds that of bulk cells. Potential consequences of these findings for chemotherapy are discussed.     

Using “Big Data” to Capture Overall Health Status: Properties and Predictive Value of a Claims-Based Health Risk Score

BackgroundInvestigators across many fields often struggle with how best to capture an individual’s overall health status, with options including both subjective and objective measures. With the increasing availability of “big data,” researchers can now take advantage of novel metrics of health status. These predictive algorithms were initially developed to forecast and manage expenditures, yet they represent an underutilized tool that could contribute significantly to health research. In this paper, we describe the properties and possible applications of one such “health risk score,” the DxCG Intelligence tool.MethodsWe link claims and administrative datasets on a cohort of U.S. workers during the period 1996–2011 (N = 14,161). We examine the risk score’s association with incident diagnoses of five disease conditions, and we link employee data with the National Death Index to characterize its relationship with mortality. We review prior studies documenting the risk score’s association with other health and non-health outcomes, including healthcare utilization, early retirement, and occupational injury.

Results and Conclusions

We find that the risk score is associated with outcomes across a variety of health and non-health domains. These examples demonstrate the broad applicability of this tool in multiple fields of research and illustrate its utility as a measure of overall health status for epidemiologists and other health researchers.     

Impact of a Participatory Intervention with Women’s Groups on Psychological Distress among Mothers in Rural Bangladesh: Secondary Analysis of a Cluster-Randomised Controlled Trial

Background

Perinatal common mental disorders (PCMDs) are a major cause of disability among women and disproportionately affect lower income countries. Interventions to address PCMDs are urgently needed in these settings, and group-based and peer-led approaches are potential strategies to increase access to mental health interventions. Participatory women’s health groups led by local women previously reduced postpartum psychological distress in eastern India. We assessed the effect of a similar intervention on postpartum psychological distress in rural Bangladesh.

Method

We conducted a secondary analysis of data from a cluster-randomised controlled trial with 18 clusters and an estimated population of 532,996. Nine clusters received an intervention comprising monthly meetings during which women’s groups worked through a participatory learning and action cycle to develop strategies for improving women’s and children’s health. There was one group for every 309 individuals in the population, 810 groups in total. Mothers in nine control clusters had access to usual perinatal care. Postpartum psychological distress was measured with the 20-item Self Reporting Questionnaire (SRQ-20) between six and 52 weeks after delivery, during the months of January to April, in 2010 and 2011.

Results

We analysed outcomes for 6275 mothers. Although the cluster mean SRQ-20 score was lower in the intervention arm (mean 5.2, standard deviation 1.8) compared to control (5.3, 1.2), the difference was not significant (β 1.44, 95% CI 0.28, 3.08).

Conclusions

Despite promising results in India, participatory women’s groups focused on women’s and children’s health had no significant effect on postpartum psychological distress in rural Bangladesh.     

Associations between women’s empowerment and child development,growth, and nurturing care practices in sub-Saharan Africa: A cross-sectional analysis of demographic and health survey data

BackgroundApproximately 40% of children 3 to 4 years of age in low- and middle-income countries have suboptimal development and growth. Women’s empowerment may help provide inputs of nurturing care for early development and growth by building caregiver capacity and family support. We examined the associations between women’s empowerment and child development, growth, early learning, and nutrition in sub-Saharan Africa (SSA).Methods and findingsWe pooled data on married women (15 to 49 years) and their children (36 to 59 months) from Demographic and Health Surveys that collected data on child development (2011 to 2018) in 9 SSA countries (N = 21,434): Benin, Burundi, Cameroon, Chad, Congo, Rwanda, Senegal, Togo, and Uganda. We constructed a women’s empowerment score using factor analysis and assigned women to country-specific quintile categories. The child outcomes included cognitive, socioemotional, literacy–numeracy, and physical development (Early Childhood Development Index), linear growth (height-for-age Z-score (HAZ) and stunting (HAZ <−2). Early learning outcomes were number of parental stimulation activities (range 0 to 6) and learning resources (range 0 to 4). The nutrition outcome was child dietary diversity score (DDS, range 0 to 7). We assessed the relationship between women’s empowerment and child development, growth, early learning, and nutrition using multivariate generalized linear models.On average, households in our sample were large (8.5 ± 5.7 members) and primarily living in rural areas (71%). Women were 31 ± 6.6 years on average, 54% had no education, and 31% had completed primary education. Children were 47 ± 7 months old and 49% were female. About 23% of children had suboptimal cognitive development, 31% had suboptimal socioemotional development, and 90% had suboptimal literacy–numeracy development. Only 9% of children had suboptimal physical development, but 35% were stunted. Approximately 14% of mothers and 3% of fathers provided ≥4 stimulation activities. Relative to the lowest quintile category, children of women in the highest empowerment quintile category were less likely to have suboptimal cognitive development (relative risk (RR) 0.89; 95% confidence interval (CI) 0.80, 0.99), had higher HAZ (mean difference (MD) 0.09; 95% CI 0.02, 0.16), lower risk of stunting (RR 0.93; 95% CI 0.87, 1.00), higher DDS (MD 0.17; 95% CI 0.06, 0.29), had 0.07 (95% CI 0.01, 0.13) additional learning resources, and received 0.16 (95% CI 0.06, 0.25) additional stimulation activities from their mothers and 0.23 (95% CI 0.17 to 0.29) additional activities from their fathers. We found no evidence that women’s empowerment was associated with socioemotional, literacy–numeracy, or physical development. Study limitations include the possibility of reverse causality and suboptimal assessments of the outcomes and exposure.ConclusionsWomen’s empowerment was positively associated with early child cognitive development, child growth, early learning, and nutrition outcomes in SSA. Efforts to improve child development and growth should consider women’s empowerment as a potential strategy.

Lilia Bliznashka and co-workers study empowerment of women and associated child health outcomes in sub-Saharan Africa.     

Clinicopathologic Analysis of Localized Nasal/Paranasal Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) comprises 2 molecularly distinct subgroups of non-germinal center B-cell-like (non-GCB) and germinal center B-cell-like (GCB) DLBCLs, with the former showing relatively poor prognosis. In the present study, we analyzed the clinicopathological features of 39 patients with localized nasal/paranasal DLBCL. Immunohistochemistry-based subclassification revealed that 11 patients (28%) were of the GCB-type according to Hans’ algorithm and 11 (28%) were of the GCB-type according to Choi’s algorithm. According to both Hans’ and Choi’s algorithms, the non-GCB type was predominant. Nevertheless, prognosis was good. Overall survival did not differ significantly between the GCB and non-GCB subgroups (Hans’ algorithm: p = 0.57, Choi’s algorithm: p = 0.99). Furthermore, the prognosis of localized nasal/paranasal DLBCL was better than that of other localized extranodal DLBCLs. The prognosis of extranodal DLBCL is usually considered poorer than that of nodal DLBCL. However, in our study, no difference was noted between patients with localized nasal/paranasal DLBCL and patients with localized nodal DLBCL. In conclusion, although the non-GCB subtype is thought to show poor prognosis, in our study, the prognosis for localized nasal/paranasal DLBCL patients was good irrespective of subclassification.     

A novel survival multifactor dimensionality reduction method for detecting gene–gene interactions with application to bladder cancer prognosis

The widespread use of high-throughput methods of single nucleotide polymorphism (SNP) genotyping has created a number of computational and statistical challenges. The problem of identifying SNP–SNP interactions in case–control studies has been studied extensively, and a number of new techniques have been developed. Little progress has been made, however, in the analysis of SNP–SNP interactions in relation to time-to-event data, such as patient survival time or time to cancer relapse. We present an extension of the two class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP–SNP interactions in the context of survival analysis. The proposed Survival MDR (Surv-MDR) method handles survival data by modifying MDR’s constructive induction algorithm to use the log-rank test. Surv-MDR replaces balanced accuracy with log-rank test statistics as the score to determine the best models. We simulated datasets with a survival outcome related to two loci in the absence of any marginal effects. We compared Surv-MDR with Cox-regression for their ability to identify the true predictive loci in these simulated data. We also used this simulation to construct the empirical distribution of Surv-MDR’s testing score. We then applied Surv-MDR to genetic data from a population-based epidemiologic study to find prognostic markers of survival time following a bladder cancer diagnosis. We identified several two-loci SNP combinations that have strong associations with patients’ survival outcome. Surv-MDR is capable of detecting interaction models with weak main effects. These epistatic models tend to be dropped by traditional Cox regression approaches to evaluating interactions. With improved efficiency to handle genome wide datasets, Surv-MDR will play an important role in a research strategy that embraces the complexity of the genotype–phenotype mapping relationship since epistatic interactions are an important component of the genetic basis of disease.     

A Novel Integrated Score Index of Echocardiographic Indices for the Evaluation of Left Ventricular Diastolic Function

Background

We propose a novel integrated score index, which could be used to quantify and grade left ventricular (LV) diastolic function.

Methods

We enrolled 629 participants [393 healthy subjects, 145 with hypertension (HTN), 24 with hypertrophic cardiomyopathy (HCM), and 67 with coronary artery disease (CAD)]. This score index was with a score of 1 for an E/A ratio < 1, a score of 1 for a septal e’/a’ ratio ≤ 0.8, a score of 2 for a lateral e’/a’ ratio ≤ 1, a score of 2 for a septal E/e’ ratio ≥10–15, a score of 3 for a lateral E/e’ ratio ≥8–15, and a score of 1 for a deceleration time >240 ms. The sum of each score was considered as the final value in this scoring method (either a septal or a lateral E/e’ ratio > 15 was given a total score of 10, regardless of the other measurements).

Results

After analysis, the AUROC of this integrated score index for predicting any diastolic dysfunction (discriminated by the American Society of Echocardiography guidelines) was 0.962, and the AUROC of the method from the logistic regression was 0.970. The mean values of the score index for the groups were 3.81 ± 0.12 in healthy, 6.48 ± 0.19 in HTN, 7.35 ± 0.46 in HCM, and 6.62 ± 0.29 in CAD. Using the score index, the healthy subjects obtained lower scores compared with those of HTN (p = 0.00), HCM (p = 0.00), and CAD (p = 0.00). Therefore, this score index could discriminate patients with diseases with impaired diastolic function from the healthy subjects when the total sum of the score was equal to or greater than 4.

Conclusions

If the presently used methods cannot allow the clear diagnosis of LV diastolic dysfunction, this integrated score index might be helpful for discriminating diseases with impaired diastolic function.     

Inhibition of MDR1 gene expression by chimeric HNA antisense oligonucleotides

Hexitol nucleic acids (HNAs) are nuclease resistant and provide strong hybridization to RNA. However, there is relatively little information on the biological properties of HNA antisense oligonucleotides. In this study, we compared the antisense effects of a chimeric HNA ‘gapmer’ oligonucleotide comprising a phosphorothioate central sequence flanked by 5′ and 3′ HNA sequences to conventional phosphorothioate oligonucleotides and to a 2′-O-methoxyethyl (2′-O-ME) phosphorothioate ‘gapmer’. The antisense oligomers each targeted a sequence bracketing the start codon of the message of MDR1, a gene involved in multi-drug resistance in cancer cells. Antisense and control oligonucleotides were delivered to MDR1-expressing cells using transfection with the cationic lipid Lipofectamine 2000. The anti-MDR1 HNA gapmer was substantially more potent than a phosphorothioate oligonucleotide of the same sequence in reducing expression of P-glycoprotein, the MDR1 gene product. HNA and 2′-O-ME gapmers displayed similar potency, but a pure HNA antisense oligonucleotide (lacking the phosphorothioate ‘gap’) was ineffective, indicating that RNase H activity was likely required. Treatment with anti-MDR1 HNA gapmer resulted in increased cellular accumulation of the drug surrogate Rhodamine 123 that correlated well with the reduced cell surface expression of P-glycoprotein. Thus, HNA gapmers may provide a valuable additional tool for antisense-based investigations and therapeutic approaches.     

Mental Health Service Use by Young People: The Role of Caregiver Characteristics

Aims

Many children and adolescents experiencing mental health problems do not receive appropriate care. Strategies to encourage appropriate access to services might be improved by a more detailed understanding of service use determinants within this group. In view of caregivers’ key role in young people’s pathways to care, this study aimed to advance understanding of caregiver-related characteristics that influence service use among young people.

Methods

We interviewed 407 primary caregivers of young people aged 9-18 years, recruited from a Greater London (United Kingdom) community sample. Caregivers reported on young people’s service use in health care sector and/or education settings, and caregivers’ intended stigmatising behaviours, help-seeking attitudes, and personal service use. Logistic regression analyses examined the relationship between these caregiver characteristics and young people’s service use, controlling for young people’s clinical and socio-demographic factors.

Results

Caregivers’ intended stigmatising behaviours in particular exerted a strong influence on young people’s service use within each service setting. The impact of this characteristic interacted with caregivers’ service use in influencing young people’s service use across health care and education settings and health care settings specifically. For young people’s service use within education settings, caregivers’ intended stigmatising behaviours score had a main effect.

Conclusions

This study highlights the key role caregivers’ attitudes and experiences hold in young people’s service use. The findings indicate that strategies aiming to bridge the gap between young people’s service needs and utilisation might be improved by targeting stigma amongst caregivers.     

Longitudinal Study of Informed Consent in Innovative Therapy Research: Experience and Provisional Recommendations from a Multicenter Trial of Intracerebral Grafting

BackgroundThere is an urgent need to assess and improve the consent process in clinical trials of innovative therapies for neurodegenerative disorders.MethodsWe performed a longitudinal study of the consent of Huntington’s disease patients during the Multicenter Fetal Cell Intracerebral Grafting Trial in Huntington’s Disease (MIG-HD) in France and Belgium. Patients and their proxies completed a consent questionnaire at inclusion, before signing the consent form and after one year of follow-up, before randomization and transplantation. The questionnaire explored understanding of the protocol, satisfaction with the information delivered, reasons for participating in the trial and expectations regarding the transplant. Forty-six Huntington’s disease patients and 27 proxies completed the questionnaire at inclusion, and 27 Huntington’s disease patients and 16 proxies one year later.ResultsThe comprehension score was high and similar for Huntington’s disease patients and proxies at inclusion (72.6% vs 77.8%; P > 0.1) but only decreased in HD patients after one year. The information satisfaction score was high (73.5% vs 66.5%; P > 0.1) and correlated with understanding in both patients and proxies. The motivation and expectation profiles were similar in patients and proxies and remained unchanged after one year.ConclusionsCognitively impaired patients with Huntington’s disease were capable of consenting to participation in this trial. This consent procedure has presumably strengthened their understanding and should be proposed before signing the consent form in future gene or cell therapy trials for neurodegenerative disorders. Because of the potential cognitive decline, proxies should be designated as provisional surrogate decision-makers, even in competent patients.     

A New Approach for Assessing Sleep Duration and Postures from Ambulatory Accelerometry

Interest in the effects of sleeping behavior on health and performance is continuously increasing–both in research and with the general public. Ecologically valid investigations of this research topic necessitate the measurement of sleep within people’s natural living contexts. We present evidence that a new approach for ambulatory accelerometry data offers a convenient, reliable, and valid measurement of both people’s sleeping duration and quality in their natural environment. Ninety-two participants (14–83 years) wore acceleration sensors on the sternum and right thigh while spending the night in their natural environment and following their normal routine. Physical activity, body posture, and change in body posture during the night were classified using a newly developed classification algorithm based on angular changes of body axes. The duration of supine posture and objective indicators of sleep quality showed convergent validity with self-reports of sleep duration and quality as well as external validity regarding expected age differences. The algorithms for classifying sleep postures and posture changes very reliably distinguished postures with 99.7% accuracy. We conclude that the new algorithm based on body posture classification using ambulatory accelerometry data offers a feasible and ecologically valid approach to monitor sleeping behavior in sizable and heterogeneous samples at home.     

Parental Weight Perceptions: A Cause for Concern in the Prevention and Management of Childhood Obesity in the United Arab Emirates

Parental participation is a key factor in the prevention and management of childhood obesity, thus parental recognition of weight problems is essential. We estimated parental perceptions and their determinants in the Emirati population. We invited 1541 students (grade 1–12; 50% boys) and their parents, but only 1440 (6–19 years) and their parents consented. Of these, 945 Emirati nationals provided data for analysis. Anthropometric and demographic variables were measured by standard methods. CDC BMI percentile charts for age and sex were used to classify children’s weight. Parental perception of their children’s weight status (underweight, normal, and overweight/obese) was recorded. Logistic regression analyses were used to identify independent predictors of parental perceptions of children’s weight status. Of all parents, 33.8% misclassified their children’s’ weight status; underestimating (27.4%) or overestimating (6.3%). Misclassification was highest among parents of overweight/obese children (63.5%) and underweight (55.1%) children. More importantly, parental perceptions of their children being overweight or obese, among truly overweight/obese children, i.e. correct identification of an overweight/obese child as such, were associated with the true child’s BMI percentile (CDC) with an OR of 1.313 (95% CI: 1.209–1.425; p<0.001) per percentile point, but not age, parental education, household income, and child’s sex. We conclude that the majority of parents of overweight/obese children either overestimated or, more commonly, underestimated children’s weight status. Predictors of accurate parental perception, in this population, include the true children’s BMI, but not age, household income, and sex. Thus, parents having an incorrect perception of their child’s weight status may ignore otherwise appropriate health messages.     

Identifying rare and common disease associated variants in genomic data using Parkinson’s disease as a model

Background

Genome-wide association studies have been successful in identifying common genetic variants for human diseases. However, much of the heritable variation associated with diseases such as Parkinson’s disease remains unknown suggesting that many more risk loci are yet to be identified. Rare variants have become important in disease association studies for explaining missing heritability. Methods for detecting this type of association require prior knowledge on candidate genes and combining variants within the region. These methods may suffer from power loss in situations with many neutral variants or causal variants with opposite effects.

Results

We propose a method capable of scanning genetic variants to identify the region most likely harbouring disease gene with rare and/or common causal variants. Our method assigns a score at each individual variant based on our scoring system. It uses aggregate scores to identify the region with disease association. We evaluate performance by simulation based on 1000 Genomes sequencing data and compare with three commonly used methods. We use a Parkinson’s disease case–control dataset as a model to demonstrate the application of our method.Our method has better power than CMC and WSS and similar power to SKAT-O with well-controlled type I error under simulation based on 1000 Genomes sequencing data. In real data analysis, we confirm the association of α-synuclein gene (SNCA) with Parkinson’s disease (p = 0.005). We further identify association with hyaluronan synthase 2 (HAS2, p = 0.028) and kringle containing transmembrane protein 1 (KREMEN1, p = 0.006). KREMEN1 is associated with Wnt signalling pathway which has been shown to play an important role for neurodegeneration in Parkinson’s disease.

Conclusions

Our method is time efficient and less sensitive to inclusion of neutral variants and direction effect of causal variants. It can narrow down a genomic region or a chromosome to a disease associated region. Using Parkinson’s disease as a model, our method not only confirms association for a known gene but also identifies two genes previously found by other studies. In spite of many existing methods, we conclude that our method serves as an efficient alternative for exploring genomic data containing both rare and common variants.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-014-0088-9) contains supplementary material, which is available to authorized users.