Trajectories of frailty among Chinese older people in Hong Kong between 2001 and 2012: an age-period-cohort analysis.

Background: there is little evidence to suggest that older people today are living in better health than their predecessors did at the same age. Only a few studies have evaluated whether there are birth cohort effects on frailty, an indicator of health in older people, encompassing physical, functional and mental health dimensions. Objectives: this study examined longitudinal trajectories of frailty among Chinese older people in Hong Kong. Methods: this study utilised data from the 18 Elderly Health Centres of the Department of Health comprising a total of 417,949 observations from 94,550 community-dwelling Chinese people aged ≥65 years in one early birth cohort (1901-23) and four later birth cohorts (1924-29, 1930-35, 1936-41, 1942-47) collected between 2001 and 2012, to examine trajectories of the frailty index and how birth cohorts may have contributed to the trends using an age-period-cohort analysis. Results: more recent cohorts had higher levels of frailty than did earlier cohorts at the same age, controlling for period, gender, marital status, educational levels, socioeconomic status, lifestyle and social factors. Older age, being female, widowhood, lower education and smoking were associated with higher levels of frailty. Conclusion: more recent cohorts had higher levels of frailty than did earlier cohorts. Frailty interventions, coupled with early detection, should be developed to combat the increasing rates of frailty in Hong Kong Chinese.

Stratified polygenic risk prediction model with application to CAGI bipolar disorder sequencing data.

Genetic data consists of a wide range of marker types, including common, low-frequency, and rare variants. Multiple genetic markers and their interactions play central roles in the heritability of complex disease. In this study, we propose an algorithm that uses a stratified variable selection design by genetic architectures and interaction effects, achieved by a dataset-adaptive W-test. The polygenic sets in all strata were integrated to form a classification rule. The algorithm was applied to the Critical Assessment of Genome Interpretation 4 bipolar challenge sequencing data. The prediction accuracy was 60% using genetic markers on an independent test set. We found that epistasis among common genetic variants contributed most substantially to prediction precision. However, the sample size was not large enough to draw conclusions for the lack of predictability of low-frequency variants and their epistasis.

Working toward precision medicine: Predicting phenotypes from exomes in the Critical Assessment of Genome Interpretation (CAGI) challenges.

Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge. Here, we discuss the range of techniques used for phenotype prediction as well as the methods used for assessing predictive models. Additionally, we outline some of the difficulties associated with making predictions and evaluating them. The lessons learned from the exome challenges can be applied to both research and clinical efforts to improve phenotype prediction from genotype. In addition, these challenges serve as a vehicle for sharing clinical and research exome data in a secure manner with scientists who have a broad range of expertise, contributing to a collaborative effort to advance our understanding of genotype-phenotype relationships.

GSA-Lightning: ultra-fast permutation-based gene set analysis.

UNLABELLED: The computational speed of many gene set analysis methods can be slow due to the computationally demanding permutation step. This article introduces GSA-Lightning, a fast implementation of permutation-based gene set analysis. GSA-Lightning achieves significant speedup compared with existing methods, particularly when the number of gene sets and permutations are large. AVAILABILITY AND IMPLEMENTATION: The GSA-Lightning R package is available on Github at https://github.com/billyhw/GSALightning and on R Bioconductor. The package also contains a comprehensive user's guide with a step-by-step tutorial vignette. CONTACT: weidong.tian@fudan.edu.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Patterns in longitudinal growth of refraction in Southern Chinese children: cluster and principal component analysis.

In the present study we attempt to use hypothesis-independent analysis in investigating the patterns in refraction growth in Chinese children, and to explore the possible risk factors affecting the different components of progression, as defined by Principal Component Analysis (PCA). A total of 637 first-born twins in Guangzhou Twin Eye Study with 6-year annual visits (baseline age 7-15 years) were available in the analysis. Cluster 1 to 3 were classified after a partitioning clustering, representing stable, slow and fast progressing groups of refraction respectively. Baseline age and refraction, paternal refraction, maternal refraction and proportion of two myopic parents showed significant differences across the three groups. Three major components of progression were extracted using PCA: "Average refraction", "Acceleration" and the combination of "Myopia stabilization" and "Late onset of refraction progress". In regression models, younger children with more severe myopia were associated with larger "Acceleration". The risk factors of "Acceleration" included change of height and weight, near work, and parental myopia, while female gender, change of height and weight were associated with "Stabilization", and increased outdoor time was related to "Late onset of refraction progress". We therefore concluded that genetic and environmental risk factors have different impacts on patterns of refraction progression.

Cataract-Related Visual Impairment Corrected by Cataract Surgery and 10-Year Mortality: The Liwan Eye Study.

PURPOSE: To assess 10-year mortality in people who had undergone cataract surgery with no residual visual impairment (VI) and those who had persistent VI due to cataract using a population-based cohort. METHODS: The Liwan Eye Study is a 10-year longitudinal study commenced in 2003. According to the World Health Organization, presenting VI was defined as visual acuity less than 20/63 in the better-seeing eye. History of cataract surgery was defined as cataract surgery performed on either eye. Information on the date of surgery was recorded. Dates of death occurring between baseline and April 30, 2014 were obtained from the National Death Index data. Information on socioeconomic factors was obtained from questionnaire interviews. Cox proportional hazards regression models were used to assess the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Fifty-nine participants had undergone cataract surgery without residual VI and 67 participants had persistent cataract-related VI. The 10-year mortality rate for participants who had undergone cataract surgery without residual VI was statistically significant lower than that in participants who had VI due to cataract based on log-rank test (32.2% vs. 64.2%; P = 0.002). This finding remained significant in the unadjusted Cox proportional hazards model (HR, 0.43; 95% CI, 0.25-0.74; P = 0.002). After adjusting for age, sex, history of diabetes, and hypertension, body mass index (BMI), education level, and personal income, participants with cataract surgery and no residual VI did not have a higher chance of survival than participants with persistent VI due to cataract (HR, 0.56; 95% CI, 0.26-1.20; P = 0.136). CONCLUSIONS: Cataract-related VI corrected by cataract surgery was not associated with better survival after adjusting for a number of possible confounders. Given our sample size is relatively small and limited power, further studies with larger sample are needed.

Trends in activities of daily living disability in a large sample of community-dwelling Chinese older adults in Hong Kong: an age-period-cohort analysis.

BACKGROUND: To examine the trends in activities of daily living (ADL) disability in older Chinese adults in Hong Kong between 2001 and 2012. METHODS: Using data from the Elderly Health Centres (EHCs) of the Department of Health comprising a total of 54 808 community-dwelling Chinese adults aged ≥65 years in 1 early cohort (1904-1917) and 10 3-year birth cohorts (1918-1920, 1921-1923, 1924-1926, 1927-1929, 1930-1932, 1933-1935, 1936-1938, 1939-1941, 1942-1944, 1945-1947), we examined trends in ADL disability by using age-period-cohort (APC) models. ADL disability was defined as being unable to perform at least 1 of 7 ADL activities (bathing, dressing, toileting, transferring, feeding, grooming, walking) independently. Cross-classified random-effects logistic regressions were performed for each of the APC trends with adjustment for age, period, cohort, sociodemographic, lifestyle, comorbidity and self-rated health. RESULTS: The mean age of the cohort was 70.9±4.7 (range 65-99) years. The prevalence rate of ADL disability was 1.6%. ADL disability increased with age (p<0.001) and the gradient of the increase was steeper in the older age groups. At the same age, women (1.7%) were more likely to report ADL disability than men (1.4%, p=0.001). For both genders, there was an increase in ADL disability between 2003 and 2012; adjustment for age, cohort and other covariates has diminished the trends observed among men. There was no cohort effect in ADL disability. CONCLUSIONS: ADL disability in older adults has increased over the last decade. Further study is required to identify possible causes behind the disability trends.

Does Myopia Affect Angle Closure Prevalence.

PURPOSE: To conduct a simulation study to estimate the prevalence of occludable angle (OA), a surrogate for primary angle closure glaucoma (PACG), with the increased rate of myopia in the Chinese population. METHODS: People with phakic eyes in Liwan Eye Study were included as the study sample. Anterior chamber depth (ACD) was measured before dilation by A-mode ultrasound and OA was evaluated with static gonioscopy. Random sampling was used to generate 50 cohorts with sample size of 200 for each of myopic rates 10%, 20%, 40%, 50%, and 135 for myopic rate 60%, according to the multinomial distribution. The mean ACD and OA rates of each cohort were calculated. Logistic function model of nonlinear least-squares estimation was used to predict the prevalence of OA. RESULTS: Data of the right eyes from 1160 subjects were qualified for analysis. The mean age was 64.2 ± 9.5 years, with 43% being male. The prevalence of myopia and OA was 32.5% (95% confidence interval [CI], 29.8%-35.3%) and 10.3% (95% CI, 8.7%-12.2%), respectively. The mean ACD in the sampling cohorts increased from 2.68 mm to 2.74 mm when the prevalence of myopia increased from 10% to 60%. The projected prevalence of OA in the cohorts with myopia prevalence of 10%, 20%, 40%, 50%, and 60% was 11.1% (95% CI, 10.5%-11.8%), 10.7% (95% CI, 10.1%-11.4%), 9.9% (95% CI, 9.3%-10.5%), 9.3% (95% CI, 8.8%-9.9%), and 9.6% (95% CI, 8.9-10.3%), respectively. CONCLUSIONS: The increasing prevalence of myopia has minimal impact on the prevalence of OA.

Association between body composition and retinal vascular caliber in children and adolescents.

PURPOSE: To elucidate the relationship between body composition and retinal vascular caliber (RVC) in children and adolescents. METHODS: Participants aged 7 to 19 years were recruited from the Guangzhou Twin Eye Study cohort. Retinal vascular caliber was measured cross-sectionally from retinal images using a computer-aided program. The data were expressed as the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE). Triceps skinfold thickness (TSFT) was measured using a skinfold caliper. Body composition was obtained through bioelectrical impedance analysis, providing fat mass (FM), fat mass index (FMI), fat-free mass (FFM), fat-free mass index (FFMI), body water mass (BWM), body water percentage (BWP), basal metabolic rate (BMR), and trunk fat percentage (TFP). RESULTS: A total of 731 participants were included. Among the younger children (7-11 years), there was no significant association between body composition and RVC (all P > 0.05). However, for the older children (12-19 years), increasing FM, FMI, TFP, TSFT, and BMI were associated with CRAE negatively (ß = -0.20, -0.68, -0.18, -0.17, and -0.48, respectively, all P < 0.05) and with CRVE positively (ß = 0.47, 1.26, 0.34, 0.37, and 0.78, respectively, all P < 0.05), after adjusting for age, sex, axial length, mean arterial blood pressure, and the fellow vascular diameter. In contrast, increase in BWP was associated with larger CRAE (ß = 0.33, P = 0.001) and smaller CRVE (ß = -0.64, P < 0.001). Similar associations also were observed in the analyses when the body composition parameters were divided into quartiles (all P < 0.05). CONCLUSIONS: In adolescents, greater body fat deposition is related to narrower retinal arterioles and wider retinal venules, and higher body water proportion is associated with retinal arterioles widening and retinal venules narrowing. Even during childhood, body composition might have an association with systemic microvasculature.

Functional-network-based gene set analysis using gene-ontology.

To account for the functional non-equivalence among a set of genes within a biological pathway when performing gene set analysis, we introduce GOGANPA, a network-based gene set analysis method, which up-weights genes with functions relevant to the gene set of interest. The genes are weighted according to its degree within a genome-scale functional network constructed using the functional annotations available from the gene ontology database. By benchmarking GOGANPA using a well-studied P53 data set and three breast cancer data sets, we will demonstrate the power and reproducibility of our proposed method over traditional unweighted approaches and a competing network-based approach that involves a complex integrated network. GOGANPA's sole reliance on gene ontology further allows GOGANPA to be widely applicable to the analysis of any gene-ontology-annotated genome.

Predictive modeling in case-control single-nucleotide polymorphism studies in the presence of population stratification: a case study using Genetic Analysis Workshop 16 Problem 1 dataset.

In this paper, we apply the gradient-boosting machine predictive model to the rheumatoid arthritis data for predicting the case-control status. QQ-plot suggests severe population stratification. In univariate genome-wide association studies, a correction factor for ethnicity confounding can be derived. Here we propose a novel strategy to deal with population stratification in the context of multivariate predictive modeling. We address the problem by clustering the subjects on the axes of genetic variations, and building a predictive model separately in each cluster. This allows us to control ethnicity without explicitly including it in the model, which could marginalize the genetic signal we are trying to discover. Clustering not only leads to more similar ethnicity groups but also, as our results show, increases the accuracy of our model when compared to the non-clustered approach. The highest accuracy is achieved with the model adjusted for population stratification, when the genetic axes of variation are included among the set of predictors, although this may be misleading given the confounding effects.