Biology subjects

Schooling, C. M.

Publications and source records attributed to Schooling, C. M..

5 recordsLinked to original sources

bioRxiv2022

Environment-wide and epigenome-wide association study of adiposity in "Children of 1997" birth cohort

BackgroundIncreasing childhood adiposity is a global issue requiring potentially local solutions to ensure it does not continue into adulthood. We systematically identified potentially modifiable targets of adiposity at the onset and end of puberty in Hong Kong the most economically developed major Chinese city. MethodsWe conducted an environment-wide association study (EWAS) and an epigenome-wide association study of adiposity to systematically assess associations with body mass index (BMI) and waist-hip ratio (WHR) in Hong Kongs population-representative "Children of 1997" birth cohort. Univariable linear regression was used to select exposures related to adiposity at ~11.5 years (BMI n[≤]7,119, WHR n=5,691) and ~17.6 years (n = 3,618) at Bonferroni-corrected significance, and multivariable linear regression to adjust for potential confounders followed by replication (n=308) and CpG by CpG analysis (n=286) at ~23 years. Findings were compared with evidence from randomized controlled trials (RCTs) and Mendelian randomization (MR) studies. ResultsAt ~11.5 and ~17.6 years the EWAS identified 14 and 37 exposures associated with BMI, as well as seven and 12 associated with WHR respectively. Most exposures had directionally consistent associations at ~23 years. Maternal second-hand smoking, maternal weight, and birth weight were consistently associated with adiposity. Diet (including dairy intake and artificially sweetened beverages), physical activity, snoring, binge eating, and earlier puberty were positively associated with BMI at ~17.6 years, while eating before sleep was inversely associated with BMI at ~17.6 years. Findings for birth weight, dairy intake, binge eating, and possibly earlier puberty are consistent with available evidence from RCTs or MR studies We found 21 CpGs related to BMI and 18 to WHR. ConclusionsThese novel insights into potentially modifiable factors associated with adiposity at the outset and the end of puberty could, if causal, inform future interventions to improve population health in Hong Kong and similar Chinese settings. FundingThis study was supported by the Health and Medical Research Fund Research Fellowship, Food and Health Bureau, Hong Kong SAR Government (#04180097). The DNA extraction was supported by CFS-HKU1.

genetics↗

bioRxiv2019

The effect of liver enzymes on body composition: a Mendelian randomization study

BackgroundHigher alanine transaminase (ALT) is positively associated with diabetes but inversely associated with body mass index (BMI) in Mendelian randomization (MR) studies, suggesting liver function may affect body composition. To clarify, we assessed the association of liver function with muscle and fat mass observationally with two-sample MR as a validation.\n\nMethodsIn the population-representative \"Children of 1997\" birth cohort, we used multivariable linear regression to assess the adjusted associations of ALT and alkaline phosphatase (ALP) (IU/L) at ~17.5 years with muscle mass (kg) and body fat percentage (%). Genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) (100% change in concentration) were applied to fat-free and fat mass (kg) in the UK Biobank (n=~331,000) to obtain unconfounded estimates using MR.\n\nResultsObservationally, ALT was positively associated with muscle mass (0.11, 95% confidence interval (CI) 0.10 to 0.12) and fat percentage (0.15, 95% CI 0.13 to 0.17). ALP was inversely associated with muscle mass (-0.03, 95% CI -0.04 to -0.02) and fat percentage (-0.02, 95% CI -0.03 to -0.01). Using MR, ALT was inversely associated with fat-free mass (-0.41, 95% CI -0.64 to -0.19) and fat mass (-0.58, 95% CI -0.85 to -0.30). ALP was not clearly associated with body composition. GGT was positively associated with fat-free (0.30, 95% CI 0.01 to 0.06) and fat mass (0.41, 95% CI 0.10 to 0.71).\n\nConclusionALT reducing fat-free mass provides a possible pathway for the positive association of ALT with diabetes, and suggests a potential target of intervention.

genetics↗

bioRxiv2019

Survival bias and competing risk can severely bias Mendelian Randomization studies of specific conditions

BackgroundMendelian randomization (MR) provides unconfounded estimates. MR is open to selection bias particularly when the underlying sample is selected on surviving the genetically instrumented exposure and other conditions that share etiology with the outcome (competing risk before recruitment). Few methods to address this bias exist. MethodsWe use directed acyclic graphs to show this selection bias can be addressed by adjusting for common causes of survival and outcome. We use multivariable MR to obtain a corrected MR estimate, specifically, the effect of statin use on ischemic stroke, because statins affect survival and stroke typically occurs later in life than ischemic heart disease so is open to competing risk. ResultsIn univariable MR the genetically instrumented effect of statin use on ischemic stroke was in a harmful direction in MEGASTROKE and the UK Biobank (odds ratio (OR) 1.33, 95% confidence interval (CI) 0.80 to 2.20). In multivariable MR adjusted for major causes of survival and ischemic stroke, (blood pressure, body mass index and smoking initiation) the effect of statin use on stroke in the UK Biobank was as expected (OR 0.81, 95% CI 0.68 to 0.98) with a Q-statistic indicating absence of genetic pleiotropy or selection bias, but not in MEGASTROKE. ConclusionMR studies concerning late onset chronic conditions with shared etiology based on samples recruited in later life need to be conceptualized within a mechanistic understanding, so as to any identify potential bias due to competing risk before recruitment, and to inform the analysis and interpretation.

genetics↗

bioRxiv2019

An evaluation of the Air Quality Health Index Program on respiratory diseases in Hong Kong: an interrupted time series analysis

BackgroundOn December 30th, 2013, the Hong Kong government implemented the Air Quality Health Index (AQHI) to reduce short-term impacts of air pollution on the population. However, whether air quality alert programs, such as the AQHI, reduce morbidity is still questionable. Using a quasi-experimental design, we conducted the first evaluation of the AQHI in Hong Kong focusing on respiratory morbidity. MethodInterrupted time series with Poisson segmented regression from 2010 to 2016 were used to detect any sudden or gradual changes in emergency respiratory hospital admissions, adjusted for air pollutants (NO2, SO2, PM10, O3), temperature and humidity, when the AQHI policy was implemented. Findings were validated using three false policy periods. We also assessed changes by specific respiratory diseases (respiratory tract infections (RTI), asthma, chronic obstructive pulmonary disease and pneumonia) and by age. ResultsFrom January 1st, 2010-December 31st, 2016, 10576.98 deseasonalized, age- and sex-standardized hospital admissions for respiratory diseases occurred in Hong Kong. On implementation of the AQHI, RTI admissions immediately dropped by 14% (relative risk (RR) 0.86 95% confidence interval (CI) 0.76-0.98). In age specific analysis, immediate reductions in hospital admissions, were only apparent in children for RTI (RR 0.84, 95% CI 0.74-0.96) and pneumonia (RR 0.88, 95% CI 0.60-0.96). ConclusionHong Kongs AQHI helped reduced hospital admissions in children, particularly for RTI and pneumonia. To maximize the health benefits of the policy, at risk groups need to be able to follow the behavioral changes recommended by the AQHI index.

epidemiology↗

bioRxiv2018

The effect of liver enzymes on adiposity: a Mendelian randomization study

Poorer liver function is positively associated with diabetes in Mendelian randomization (MR) studies. Observationally, adiposity is associated with poorer liver function. To clarify the etiology, we assessed the association of liver function with adiposity observationally and using two sample MR for validation.\n\nIn the \"Children of 1997\" birth cohort, we used multivariable linear regression to assess the associations of ALT and alkaline phosphatase (ALP) (IU/L) at [~]17.5 years with body mass index (BMI) (kg/m2). Using MR, genetic variants predicting ALT, ALP and gamma glutamyltransferase (GGT) (100% change in concentration), were applied to genome-wide association studies of BMI, waist circumference (WC) and waist-hip ratio (WHR) (standard deviations) to obtain unconfounded inverse-variance weighting estimates.\n\nObservationally, ALT was positively associated with BMI (0.10, 95% confidence interval (CI) 0.09 to 0.11). ALP was inversely associated with BMI (-0.018, 95% CI -0.024 to -0.012). Using MR, ALT was inversely associated with BMI (-0.14, 95% CI -0.20 to -0.07), but not WC or WHR. ALP and GGT were unrelated to adiposity.\n\nPoorer liver function might not cause adiposity; instead higher ALT might reduce BMI. Whether ALT contributes to diabetes by reducing muscle mass, given the no association of ALT with WC or WHR, requires investigation.\n\nAbbreviations

epidemiology↗