An atlas of genetic scores to predict multi-omic traits.

The use of omic modalities to dissect the molecular underpinnings of common diseases and traits is becoming increasingly common. But multi-omic traits can be genetically predicted, which enables highly cost-effective and powerful analyses for studies that do not have multi-omics1. Here we examine a large cohort (the INTERVAL study2; n = 50,000 participants) with extensive multi-omic data for plasma proteomics (SomaScan, n = 3,175; Olink, n = 4,822), plasma metabolomics (Metabolon HD4, n = 8,153), serum metabolomics (Nightingale, n = 37,359) and whole-blood Illumina RNA sequencing (n = 4,136), and use machine learning to train genetic scores for 17,227 molecular traits, including 10,521 that reach Bonferroni-adjusted significance. We evaluate the performance of genetic scores through external validation across cohorts of individuals of European, Asian and African American ancestries. In addition, we show the utility of these multi-omic genetic scores by quantifying the genetic control of biological pathways and by generating a synthetic multi-omic dataset of the UK Biobank3 to identify disease associations using a phenome-wide scan. We highlight a series of biological insights with regard to genetic mechanisms in metabolism and canonical pathway associations with disease; for example, JAK-STAT signalling and coronary atherosclerosis. Finally, we develop a portal ( https://www.omicspred.org/ ) to facilitate public access to all genetic scores and validation results, as well as to serve as a platform for future extensions and enhancements of multi-omic genetic scores.

Development and validation of a lifestyle risk index to screen for metabolic syndrome and its components in two multi-ethnic cohorts.

BACKGROUND: Metabolic syndrome (MetS) is a precursor to cardiovascular diseases and type 2 diabetes. Existing MetS prediction models relied heavily on biochemical measures and those based on non-invasive predictors such as lifestyle behaviours were limited. We aim to (1) develop a weighted lifestyle risk index for MetS and (2) externally validate this index using two Asian-based cohorts in Singapore. METHODS: Using data from the Multi-Ethnic Cohort (MEC) 1 (n = 2873, 41% male), multiple logistic regression was used to identify predictors associated with MetS. A weighted lifestyle risk index was generated using coefficients of the selected predictors in the development cohort (MEC1). Subsequently, the performance of the lifestyle risk index in predicting the occurrence of MetS within 10 years was assessed by discrimination and calibration in an external validation cohort (MEC2) (n = 6070, 43% male). RESULTS: A lifestyle risk index for MetS with nine predictors was developed (age, sex, ethnicity, having a family history of diabetes, BMI, diet, physical activity, smoking status, and screen time). This index demonstrated acceptable discrimination in the development cohort [AUC (95% CI) = 0.74 (0.71, 0.76)] and the validation cohort [AUC (95% CI) = 0.79 (0.77, 0.81)]. CONCLUSION: This lifestyle risk index exhibits potential for risk stratification in population-based screening programmes. Future research could apply a similar methodology to develop disease-specific lifestyle risk indices using nationwide registry-based data.

Association of diet quality with hand grip strength weakness and asymmetry in a multi-ethnic Asian cohort.

Hand grip strength (HGS) is an important diagnostic tool for sarcopenia and a reliable predictor for age-related chronic diseases and mortality. Interventions in nutrition have been shown as a low-cost strategy to maintain muscular strength and mass. However, there are limited data on the effect of diet on HGS in Southeast Asian populations. This study aims to investigate the association of diet quality with HGS weakness and asymmetry in a multi-ethnic population in Singapore. This cross-sectional study used data from the Singapore Multi-Ethnic Cohort (n = 1547). Dietary data were collected using a validated semi-quantitative FFQ and summarised as the Dietary Quality Index - International (DQI-I). HGS was calculated as the maximum value of six measurements from both hands. HGS weakness and asymmetry were defined using well-recognised criteria. Multivariable linear regression and logistic regression were utilised for continuous and binary outcomes, respectively, adjusting for age, sex, ethnicity, physical activity and smoking status. It was found that the highest quartile of DQI-I was significantly associated with higher HGS (ß = 1·11; 95 % CI 0·41, 1·82; Pfor trend < 0·001) and lower odds of HGS asymmetry (OR = 0·71; 95 % CI 0·53, 0·94; Pfor trend = 0·035) and both HGS weakness and asymmetry (OR = 0·50; 95 % CI 0·32, 0·76; Pfor trend = 0·004). Among the different components of DQI-I, only dietary adequacy was significantly associated with higher HGS (Pfor trend < 0·001) and lower odds for both HGS weakness and asymmetry (Pfor trend = 0·006). Our findings support that DQI-I, an indicator of overall diet quality, can be used to provide dietary guidelines for prevention and management of muscle wasting, sarcopenia and frailty.

Ecological momentary assessment of digital food and beverage marketing exposure and impact in young adults: A feasibility study.

Unhealthy food marketing is contributing to the obesity epidemic, but real-time insights into the mechanisms of this relationship are under-studied. Digital marketing is growing and following food and beverage (F&B) brands on social media is common, but measurement of exposure and impact of such marketing presents novel challenges. Thus, this study aimed to evaluate the feasibility of collecting data on exposure and impact of digital F&B marketing (DFM) using a smartphone-based ecological momentary assessment (EMA) methodology. We hypothesized that DFM-induced food cravings would vary based on whether (or not) participants engaged with F&B brands online. Participants were Singapore residents (n = 95, 21-40 years), recruited via telephone from an existing cohort. Participants were asked to upload screenshots of all sightings of online F&B marketing messages for seven days, and answer in-app contextual questions about sightings including whether any cravings were induced. Participants provided a total of 1310 uploads (median 9 per participant, Q1-Q3: 4-21) of F&B marketing messages, 27% of which were provided on Day 1, significantly more than on other days (P < 0.001). Followers of food/beverage brands on social media encountered 25.6 percentage points (95% CI 11.4, 39.7) more marketing messages that induced cravings than participants who were not followers. University education was also associated with more (18.1 percentage points; 95% CI 3.1, 33.1) encounters with marketing messages that induced cravings. It was practical and acceptable to participants to gather insights into digital F&B marketing exposure and impact using EMA in young adults, although a shorter study period is recommended in future studies. Followers of food and beverage brands on social media appear to be more prone to experience cravings after exposure to digital F&B marketing.

Isocaloric Substitution of Plant-Based Protein for Animal-Based Protein and Cardiometabolic Risk Factors in a Multiethnic Asian Population.

BACKGROUND: Evidence is accumulating that intake of animal-based and plant-based proteins has different effects on cardiometabolic health, but less is known about the health effect of isocaloric substitution of animal-based and plant-based proteins. Data from Asian populations are limited. OBJECTIVES: This study aimed to evaluate the effects of isocaloric substitution of total plant-based proteins for total and various animal-based protein food groups and to evaluate the effects of substituting protein from legumes and pulses for various animal-based protein food groups on cardiovascular disease (CVD) risk factors and predicted 10-y CVD risk. METHODS: We conducted a cross-sectional analysis using data collected from 9211 Singapore residents (aged 21-75 y) from the Singapore Multi-Ethnic Cohort. Data on sociodemographic and lifestyle factors were collected using questionnaires. Dietary intakes were assessed using a validated FFQ. BMI, waist circumference, and blood pressure were measured during a physical examination, and blood samples were collected to measure lipid profiles. Associations were assessed by substitution models using a multiple linear regression analysis. RESULTS: Isocaloric substitution of total plant-based proteins for total and all specific animal-based protein food groups were associated with lower BMI (ß: -0.30; 95% CI: -0.38, -0.22), waist circumference (ß: -0.85; 95% CI: -1.04, -0.66), and LDL cholesterol concentrations (ß: -0.06; 95% CI: -0.08, -0.05) (P < 0.0056). Replacement of processed meat and processed seafood proteins with total plant-based proteins was associated with improvement in most CVD risk factors and predicted 10-y CVD risk. Replacement of oily fish with legume proteins was associated with lower HDL cholesterol and higher TG concentrations. CONCLUSIONS: The substitution of plant-based proteins for animal-based proteins, especially from processed meat and processed seafood, was inversely associated with the established CVD risk factors such as BMI, waist circumference, and lipid concentrations and predicted 10-y CVD risk. These findings warrant further investigation in independent studies in other Asian populations.

Effects of dietary quality, physical activity and weight loss on glucose homeostasis in persons with and without prediabetes in the PREMIER trial.

AIMS: We examined the contribution of changes in diet quality, physical activity and weight loss to improvements in insulin resistance (HOMA-IR index) and fasting glucose concentrations in a long-term behavioural trial. Furthermore, we compared the effects of lifestyle changes on glycaemic markers for individuals with and without prediabetes. MATERIALS AND METHODS: The PREMIER trial was an 18-month parallel randomized trial of the impact of behavioural lifestyle interventions implementing lifestyle recommendations (dietary changes, physical activity, moderate weight loss) in adults with prehypertension or stage 1 hypertension. We analysed data on 685 men and women without diabetes. Data on body weight, fitness (treadmill test), dietary intake (24-h recalls) and glycaemic outcomes were collected at baseline and at 6 and 18 months. We used general linear models to assess the association between the exposure variables and glycaemic markers. RESULTS: The mean (SD) age was 49.9 (8.8) years, the mean (SD) body mass index was 32.9 (5.7) kg/m2 , and 35% had prediabetes at baseline. Weight loss and improvements in fitness and diet quality were each significantly associated with lower HOMA-IR and fasting glucose concentrations at 6 and 18 months. Mediation analysis indicated that the effects of fitness and diet quality were partly mediated by weight loss, but significant direct effects of diet and fitness (independent of weight changes) were also observed. Furthermore, insulin sensitivity and fasting glucose improved significantly in participants with and without prediabetes. CONCLUSIONS: Our findings indicate that behavioural lifestyle interventions can substantially improve glucose metabolism in persons with and without prediabetes and that the effects of diet quality and physical activity are partly independent of weight loss.

Association between nutrition and cognition in a multi-ethnic cohort from Singapore.

BACKGROUND: Nutrition, a modifiable risk factor, presents a low-cost prevention strategy to reduce the burden of cognitive impairment and dementia. However, studies examining the effects of dietary patterns on cognition are lacking in multi-ethnic Asian populations. We investigate the association between diet quality, measured with the Alternative Healthy Eating Index (AHEI)-2010, and cognitive impairment in middle-aged and older adults of different ethnicities (Chinese, Malay, Indian) in Singapore. METHODS: This cross-sectional study (n = 3138; mean age: 50.4 ± 9.8, 58.4% women) was based on data from the Singapore Multi-Ethnic Cohort. Dietary intake collected with a validated semi-quantitative Food Frequency Questionnaire was converted into AHEI-2010 scores. Cognition, assessed with the Mini-Mental State Examination (MMSE), was analysed as a continuous or binary outcome (cognitively impaired or not, using cut-offs of ≥ 24, 26 or 28 for no education, primary school education and secondary school education and above). Multivariable linear and logistic regression models were used to examine associations between AHEI-2010 and cognition, adjusting for covariates. RESULTS: A total of 988 (31.5%) participants had cognitive impairment. Higher AHEI-2010 scores were significantly associated with higher MMSE scores [ß = 0.44; 95% confidence interval (CI) 0.22-0.67 highest vs. lowest quartile; p-trend < 0.001] and lower odds of cognitive impairment [OR 0.69; 95% CI 0.54-0.88; p-trend = 0.01] after adjusting for all the covariates. No significant associations were observed for individual dietary components of the AHEI-2010 with MMSE or cognitive impairment. CONCLUSION: Healthier dietary patterns were associated with better cognitive function in middle-aged and older Singaporeans. These findings could inform better support to promote healthier dietary patterns in Asian populations.

Characterisation of protein-truncating and missense variants in PALB2 in 15 768 women from Malaysia and Singapore.

BACKGROUND: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population. METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays. RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks. CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

Measuring social desirability bias in a multi-ethnic cohort sample: its relationship with self-reported physical activity, dietary habits, and factor structure.

BACKGROUND: Social desirability bias is one of the oldest forms of response bias studied in social sciences. While individuals may feel the need to fake good or bad answers in response to sensitive or intrusive questions, it remains unclear how rampant such a bias is in epidemiological research pertaining to self-reported lifestyle indicators in a multicultural Asian context. The main purpose of the current study is, therefore, to examine the sociodemographic correlates and impact of social desirability responding on self-reported physical activity and dietary habits at an epidemiological scale in a non-western multi-cultural Asian setting. METHODS: Prior to the main analyses, confirmatory and exploratory factor analyses were conducted to determine the factorial validity of a western derived concept of social desirability. Multiple regression analyses were conducted on cross-sectional data (n = 2995) extracted from a nationwide survey conducted between 2019 and 2020. RESULTS: A unique factor structure of social desirability was found and was therefore used for subsequent analyses. Multiple regression analyses revealed older age groups, the Indian ethnic group, those with past or present marriages, and having no income, had a significantly greater tendency to act on the bias. CONCLUSION: The construct of social desirability bias was fundamentally different in a multicultural context than previously understood. Only a small proportion of variance of self-report lifestyle scores was explained by social desirability, thus providing support for data integrity.

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

Minimally invasive testing for early detection of lung cancer to improve patient survival is a major unmet clinical need. This study aimed to develop and validate a serum multi-microRNA (multimiR) panel as a minimally invasive test for early detection of nonsmall cell lung cancer (NSCLC) regardless of smoking status, gender, and ethnicity. Our study included 744 NSCLC cases and 944 matched controls, including smokers and nonsmokers, male and female, with Asian and Caucasian subjects. Using RT-qPCR and a tightly controlled workflow, we quantified the absolute expression of 520 circulating microRNAs (miRNAs) in a Chinese cohort of 180 early stage NSCLC cases and 216 healthy controls (male smokers). Candidate biomarkers were verified in two case-control cohorts of 432 Chinese and 218 Caucasians, respectively (including females and nonsmokers). A multimiR panel for NSCLC detection was developed using a twofold cross-validation and validated in three additional Asian cohorts comprising 642 subjects. We discovered 35 candidate miRNA biomarkers, verified 22 of them, and developed a five-miR panel that detected NSCLC with area under curve (AUC) of 0.936-0.984 in the discovery and verification cohorts. The panel was validated in three independent cohorts with AUCs of 0.973, 0.916, and 0.917. The sensitivity of five-miR test was 81.3% for all stages, 82.9% for stages I and II, and 83.0% for stage I NSCLC, when the specificity is at 90.7%. We developed a minimally invasive five-miR serum test for detecting early stage NSCLC and validated its performance in multiple patient cohorts independent of smoking status, gender, and ethnicity.

Evaluating the Effects of Rewards and Schedule Length on Response Rates to Ecological Momentary Assessment Surveys: Randomized Controlled Trials.

BACKGROUND: Ecological momentary assessments (EMAs) are short, repeated surveys designed to collect information on experiences in real-time, real-life contexts. Embedding periodic bursts of EMAs within cohort studies enables the study of experiences on multiple timescales and could greatly enhance the accuracy of self-reported information. However, the burden on participants may be high and should be minimized to optimize EMA response rates. OBJECTIVE: We aimed to evaluate the effects of study design features on EMA response rates. METHODS: Embedded within an ongoing cohort study (Health@NUS), 3 bursts of EMAs were implemented over a 7-month period (April to October 2021). The response rate (percentage of completed EMA surveys from all sent EMA surveys; 30-42 individual EMA surveys sent/burst) for each burst was examined. Following a low response rate in burst 1, changes were made to the subsequent implementation strategy (SMS text message announcements instead of emails). In addition, 2 consecutive randomized controlled trials were conducted to evaluate the efficacy of 4 different reward structures (with fixed and bonus components) and 2 different schedule lengths (7 or 14 d) on changes to the EMA response rate. Analyses were conducted from 2021 to 2022 using ANOVA and analysis of covariance to examine group differences and mixed models to assess changes across all 3 bursts. RESULTS: Participants (N=384) were university students (n=232, 60.4% female; mean age 23, SD 1.3 y) in Singapore. Changing the reward structure did not significantly change the response rate (F3,380=1.75; P=.16). Changing the schedule length did significantly change the response rate (F1,382=6.23; P=.01); the response rate was higher for the longer schedule (14 d; mean 48.34%, SD 33.17%) than the shorter schedule (7 d; mean 38.52%, SD 33.44%). The average response rate was higher in burst 2 and burst 3 (mean 50.56, SD 33.61 and mean 48.34, SD 33.17, respectively) than in burst 1 (mean 25.78, SD 30.12), and the difference was statistically significant (F2,766=93.83; P<.001). CONCLUSIONS: Small changes to the implementation strategy (SMS text messages instead of emails) may have contributed to increasing the response rate over time. Changing the available rewards did not lead to a significant difference in the response rate, whereas changing the schedule length did lead to a significant difference in the response rate. Our study provides novel insights on how to implement EMA surveys in ongoing cohort studies. This knowledge is essential for conducting high-quality studies using EMA surveys. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/ct2/show/NCT05154227.

Taste of Modern Diets: The Impact of Food Processing on Nutrient Sensing and Dietary Energy Intake.

BACKGROUND: Both fresh and processed foods are available in the modern food environment where taste can signal presence of nutrients. However, whether these taste-nutrient relationships are maintained across different degrees of food processing is not well understood, and less is known about the relative contribution of different taste qualities to population energy intakes. OBJECTIVES: To investigate the association between perceived intensity of 6 taste modalities and a food's nutrient content in the context of food processing and to further examine the relative contribution of different taste clusters to total energy intakes, stratified by weight status. METHODS: Diet and lifestyle data from the Singapore Multi-Ethnic Cohort Phase 2 (N = 7011; aged 21-75 y) were collected through interviewer-administrated questionnaires. Taste and nutrient profiles for each of the 269 Singaporean foods were derived using a published taste database and food composition table. Each food was then categorized into the NOVA food-processing classification (unprocessed, processed, ultra-processed) to compare the strength of taste-nutrient relationships. Multivariable-adjusted models were used to examine associations between relative consumption of foods from different taste clusters and processing categories, energy intake, and BMI (in kg/m2) within a population cohort. RESULTS: Sweet taste and mono- and disaccharide content of foods were significantly associated across all processing categories, although this association was weaker among ultra-processed foods (UPFs) (r = 0.42) than among unprocessed foods (r = 0.72). In contrast, associations between fat sensation and fat content (r = 0.74), as well as salt taste and sodium content (r = 0.84), were stronger for UPFs. Individuals who had higher energy intakes or were overweight (BMI >23) derived significantly greater percentage of energy from processed foods rather than UPFs, and this energy was higher from "savory-fatty" and lower from "neutral" tasting foods than those with lower energy intakes and normal weight (all P < 0.001). Eighty percent of individuals' dietary energy was from both "savory-fatty" and "neutral" foods, independent of differences in total energy intake and weight status. CONCLUSIONS: Taste-nutrient relationships are maintained across different degrees of food processing. Greater consumption of foods that have a high "savory-fatty" taste was associated with increased energy intakes and overweight in the Asian population.

Evaluation of Combinations of Nudging, Pricing, and Labeling Strategies to Improve Diet Quality: A Virtual Grocery Store Experiment Employing a Multiphase Optimization Strategy.

BACKGROUND: Several intervention strategies have been shown to improve diet quality. However, there is limited evidence on the increase in effectiveness that may be achieved through select combinations of these strategies. PURPOSE: This study aimed to identify an effective multicomponent intervention to improve diet quality of a grocery basket by applying a Multiphase Optimization Strategy framework and testing various combinations of four promising strategies using a fully functional web-based grocery store: (i) front-of-pack food labels and real-time feedback of the healthiness of the shoppers' grocery basket, (ii) a tax, (iii) ordering products by a nutritional quality score, and (iv) healthier substitute offers. METHODS: We conducted a hypothetical shopping study (N = 756) with a randomized full factorial design (16 conditions) to estimate main and interaction effects of the four interventions. RESULTS: The "food labels & real-time feedback" and "ordering" strategies had significantly positive main effects on overall diet quality of the shopping basket (both at p < .001). We found no effects on diet quality for the "tax" and "healthier substitute offers." None of the two-way interaction effects for different strategies on overall diet quality and nutrients were significant. CONCLUSIONS: Having "food labels & real-time feedback" and "ordering" simultaneously seemed to be more effective at improving diet quality, compared to having only one of these interventions. These results suggest that a combination of food labels with real-time feedback and ordering interventions can be part of a promising multicomponent strategy to improve diet quality in online shopping platforms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04632212.

Dietary patterns and predicted 10-year cardiovascular disease risk in a multiethnic Asian population.

BACKGROUND AND AIMS: Studies examining associations between dietary patterns and Framingham risk score (FRS) and predicted 10-year cardiovascular diseases (CVD) risk in an Asian population are lacking. This study aimed to identify a posteriori dietary patterns across three major ethnic groups in Singapore and ascertain their associations with locally modified FRS and predicted 10-year CVD risk. METHODS AND RESULTS: This cross-sectional study included 8594 Singapore residents (aged 21-75 years) from the Singapore Multi-Ethnic Cohort. Data on sociodemographic and lifestyle factors were collected via questionnaires. Food consumption was assessed using a validated Food Frequency Questionnaire. Dietary patterns were identified using principal component analysis and associations with CVD risk factors, FRS and predicted CVD risk (%) were analysed using multiple linear and logistic regression. Four dietary patterns emerged that explained 25.6% of variance. The 'processed food and sugar-sweetened beverages' pattern was significantly associated with higher FRS (ß: 0.13; 95% CI: 0.04, 0.23), while the 'ethnic breads, legumes and nuts' (ß: 0.13; 95% CI: 0.22, -0.04) and 'whole grains, fruit and dairy' (ß: 0.17; 95% CI: 0.24, -0.10) patterns were significantly associated with lower FRS. The 'meat and vegetables' pattern was not significantly associated with FRS. Increased adherence to the 'whole grains, fruit and dairy' pattern was associated with lower odds of having predicted CVD risk of ≥10% (p-trend: 0.03). CONCLUSION: Adherence to the 'ethnic breads, legumes and nuts' and 'whole grains, fruit and dairy' patterns was associated with a lower predicted CVD risk, and an inverse association for the 'processed food and sugar-sweetened beverages' pattern in an Asian population. These findings can inform the development of culturally sensitive dietary interventions to prevent CVD.

"You know what, I'm in the trend as well" - Understanding the inter-play between digital and real-life social influences on the food and activity choices of young adults.

OBJECTIVE: To understand young adults' perceptions of online and real-life social influences on their food and activity choices. DESIGN: A qualitative study involving seven focus groups. Thematic analyses using both deductive and inductive techniques were performed. SETTING: A polytechnic and a university in Singapore. PARTICIPANTS: A total of 46 full-time students, 19-24 years of age. RESULTS: Participants revealed that social media meets multiple needs, contributing to its ubiquitous use and facilitating content spread between social networks. Food-related content shared on social media were mostly commercial posts, marketing foods and eateries showcasing price-promotions, emphasizing sensory properties of foods, or creating narratives that activated trends. Subsequently, real-life social activities frequently revolve around marketed foods that were not necessarily healthy. In contrast, physical activity posts were rarely being followed up in real life. Portrayals describing a toxic gym culture could contribute to negative perceptions of peers' physical activity posts and a disinclination towards sharing such posts. Participants expressed that close, supportive social networks in real-life strongly influenced initiating and maintaining healthy lifestyles. However, in a society that highly values academic achievements, participants prioritized studying and socializing over healthy eating and physical activity. CONCLUSIONS: Overall, our findings reveal that virtual and real-life social influences have complex interactions affecting Asian young adults' behavioral choices and should be considered when designing interventions for this group. Regulations related to the digital marketing of unhealthy food, and improving the availability, accessibility, and affordability of healthier food options, particularly in the foodservice sector, would be of value to consider.

Acceptance of healthy lifestyle nudges in the general population of Singapore.

BACKGROUND: In recent years, behaviourally driven policies such as nudges have been increasingly implemented to steer desired outcomes in public health. This study examines the different nudges and the socio-demographic characteristics and lifestyle behaviours that are associated with public acceptance of lifestyle nudges. METHODS: The study used data from the nationwide Knowledge, Attitudes and Practices study (KAP) on diabetes in Singapore. Three types of nudges arranged in increasing order of intrusiveness were examined: (1) information government campaigns, (2) government mandated information and (3) default rules and choice architecture. Acceptance was assessed based upon how much respondents 'agreed' with related statements describing heathy lifestyle nudges. Multivariable linear regressions were performed with socio-demographics and lifestyle behaviours using scores calculated for each nudge. RESULTS: The percentage of respondents who agreed to all statements related to each nudge were: 75.9% (information government campaigns), 73.0% (government mandated information), and 33.4% (default rules and choice architecture). Respondents of Malay/Others ethnicity (vs. Chinese) were more likely to accept information government campaigns. Respondents who were 18 - 34 years old (vs 65 years and above), female, of Malay/Indian ethnicity (vs Chinese), were sufficiently physically active, and with a healthier diet based on the DASH (Dietary Approach to Stop Hypertension) score were more likely to accept nudges related to government mandated information. Respondents of Malay/Indian ethnicity (vs Chinese), and who had a healthier diet were more likely to accept default rules and choice architecture. CONCLUSION: Individuals prefer less intrusive approaches for promoting healthy lifestyle. Ethnicity and lifestyle behaviours are associated with acceptance of nudges and should be taken into consideration during the formulation and implementation of behaviourally informed health policies.

Sources of information on diabetes and its demographic correlates: a nationwide survey among Singapore residents.

Diabetes is a major public health concern in Singapore, and the Singapore Government declared a 'War on Diabetes', which included a nationwide public health campaign. It is important to identify what sources of diabetes information reach the general population, whether this differs by socio-demographic characteristics and if the sources of information influence knowledge of diabetes to aid the successful dissemination of health information. Two thousand eight hundred ninety-five respondents were part of a population-based cross-sectional study conducted from February 2019 to September 2020. Respondents rated on a five-point scale whether they had obtained information on diabetes from eight different information sources, and responses were dichotomized into 'endorsed receiving information' or 'not endorsed receiving information'. Poisson regression models were conducted with the 'endorsement of receiving information' from each source as the outcome and socio-demographic variables as predictors. 95.9% of the study population had received information on diabetes from at least one source, and the mean number of sources was 4.2 ± 2.0. The leading source was media articles (82.1%), followed by health promotion videos/advertisements (77.9%), online websites (58.5%), books (56.5%), healthcare professionals (55.0%), radio (54.4%), public forums (27.7%) and support groups (15.5%). Endorsing a greater number of informational sources was associated with being younger, belonging to Malay or Indian instead of Chinese ethnicity, and having diabetes. An intensive nationwide diabetes awareness campaign successfully reached the public in Singapore with specific sources of information depending on socio-demographic characteristics. Findings suggest that diabetes information campaigns should utilize multiple channels for dissemination considering the different socio-demographic subgroups.

Epidemiological and ES cell-based functional evaluation of BRCA2 variants identified in families with breast cancer.

The discovery of high-risk breast cancer susceptibility genes, such as Breast cancer associated gene 1 (BRCA1) and Breast cancer associated gene 2 (BRCA2) has led to accurate identification of individuals for risk management and targeted therapy. The rapid decline in sequencing costs has tremendously increased the number of individuals who are undergoing genetic testing world-wide. However, given the significant differences in population-specific variants, interpreting the results of these tests can be challenging especially for novel genetic variants in understudied populations. Here we report the characterization of novel variants in the Malaysian and Singaporean population that consist of different ethnic groups (Malays, Chinese, Indian, and other indigenous groups). We have evaluated the functional significance of 14 BRCA2 variants of uncertain clinical significance by using multiple in silico prediction tools and examined their frequency in a cohort of 7840 breast cancer cases and 7928 healthy controls. In addition, we have used a mouse embryonic stem cell (mESC)-based functional assay to assess the impact of these variants on BRCA2 function. We found these variants to be functionally indistinguishable from wild-type BRCA2. These variants could fully rescue the lethality of Brca2-null mESCs and exhibited no sensitivity to six different DNA damaging agents including a poly ADP ribose polymerase inhibitor. Our findings strongly suggest that all 14 evaluated variants are functionally neutral. Our findings should be valuable in risk assessment of individuals carrying these variants.

The Effect of Coconut Oil Consumption on Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: Coconut oil is high in saturated fat and may, therefore, raise serum cholesterol concentrations, but beneficial effects on other cardiovascular risk factors have also been suggested. Therefore, we conducted a systematic review of the effect of coconut oil consumption on blood lipids and other cardiovascular risk factors compared with other cooking oils using data from clinical trials. METHODS: We searched PubMed, SCOPUS, Cochrane Registry, and Web of Science through June 2019. We selected trials that compared the effects of coconut oil consumption with other fats that lasted at least 2 weeks. Two reviewers independently screened articles, extracted data, and assessed the study quality according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The main outcomes included low-density lipoprotein cholesterol (LDL-cholesterol), high-density lipoprotein cholesterol (HDL-cholesterol), total cholesterol, triglycerides, measures of body fatness, markers of inflammation, and glycemia. Data were pooled using random-effects meta-analysis. RESULTS: 16 articles were included in the meta-analysis. Results were available from all trials on blood lipids, 8 trials on body weight, 5 trials on percentage body fat, 4 trials on waist circumference, 4 trials on fasting plasma glucose, and 5 trials on C-reactive protein. Coconut oil consumption significantly increased LDL-cholesterol by 10.47 mg/dL (95% CI: 3.01, 17.94; I2 = 84%, N=16) and HDL-cholesterol by 4.00 mg/dL (95% CI: 2.26, 5.73; I2 = 72%, N=16) as compared with nontropical vegetable oils. These effects remained significant after excluding nonrandomized trials, or trials of poor quality (Jadad score <3). Coconut oil consumption did not significantly affect markers of glycemia, inflammation, and adiposity as compared with nontropical vegetable oils. CONCLUSIONS: Coconut oil consumption results in significantly higher LDL-cholesterol than nontropical vegetable oils. This should inform choices about coconut oil consumption.

Quality diet indexes and risk of hepatocellular carcinoma: Findings from the Singapore Chinese Health Study.

There is limited research on the effect of dietary quality on hepatocellular carcinoma (HCC) risk in populations with relatively high risk of HCC. Using data from Singapore Chinese Health Study, a prospective cohort study, of 63 257 Chinese aged 45 to 74, we assessed four diet-quality index (DQI) scores: the Alternative Health Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet (aMED), Dietary Approaches to Stop Hypertension (DASH) and Heathy Diet Indicator (HDI). We identified 561 incident HCC cases among the cohort participants after a mean of 17.6 years of follow-up. Cox proportional hazard regression model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for HCC in relation to these DQI scores. Unconditional logistic regression method was used to evaluate the associations between DQIs and HCC risk among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg). High scores of AHEI-2010, aMED and DASH, representing higher dietary quality, were associated with lower risk of HCC (all Ptrend < .05). Compared with the lowest quartile, HRs (95% CIs) of HCC for the highest quartile of AHEI-2010, aMED and DASH were 0.69 (0.53-0.89), 0.70 (0.52-0.95) and 0.67 (0.51-0.87), respectively. No significant association between HDI and HCC risk was observed. Among HBsAg-negative individuals, similar inverse associations were observed, and the strongest inverse association was for aMED (HRQ4vsQ1 = 0.46, 95% CI: 0.23-0.94, Ptrend = .10). These findings support the notion that adherence to a healthier diet may lower the risk of HCC, suggesting that dietary modification may be an effective approach for primary prevention of HCC.