Association of genetic variants with body-mass index and blood pressure in adolescents : a replication study

The strong correlation between adiposity and blood pressure (BP) might be explained in part by shared genetic risk factors. A recent study identified three nucleotide variants [rs16933812 (PAX5), rs7638110 (MRPS22), and rs9930333 (FTO)] associated with both body mass index (BMI) and systolic blood pressure (SBP) in adolescents age 12–18years. We attempted to replicate these findings in a sample of adolescents of similar age. A total of 713 adolescents were genotyped and had anthropometric indicators and blood pressure measured at age 13, 15, 17, and 24years. Using linear mixed models, we assessed associations of these variants with BMI and SBP. In our data, rs9930333 (FTO) was associated with body mass index, but not systolic blood pressure. Neither rs16933812 (PAX5) nor rs7638110 (MRPS22) were associated with body mass index or systolic blood pressure. Although, differences in phenotypic definitions and in genetic architecture across populations may explain some of the discrepancy across studies, nucleotide variant selection in the initial study may have led to false-positive results that could not be replicated

Revisiting trajectories of BMI in youth : an in‐depth analysis of differences between BMI and other adiposity measures

Objective Body mass index (BMI) is used to identify trajectories of adiposity in youth, but it does not distinguish fat- from fat-free-mass. There are other inexpensive measures of adiposity which might better capture fat-mass in youth The objective of this study is to examine differences between sex-specific trajectories of BMI and other adiposity indicators (subscapular and triceps skinfold thickness, waist circumference, waist-to-height ratio) which may better capture fat-mass in youth. Methods Data come from four cycles of a longitudinal cohort of 1293 students in Montréal, Canada at ages 12, 15, 17 and 24. Group-based trajectory models identified sex-specific adiposity trajectories among participants with data in ≥3 cycles (n = 417 males; n = 445 females). Results There were six trajectory groups in males and females for all five indicators, except for waist circumference (seven) in both sexes and triceps skinfold thickness (four) and waist-to-height ratio (five) in females. Most trajectories indicated linear increases; only the skinfold thickness indicators identified a decreasing trajectory. While all indicators identified a trajectory with high levels of adiposity, they differed in the number and relative size of trajectories pertaining to individuals in lower half of the adiposity distribution. Conclusion BMI is a satisfactory indicator of adiposity in youth if the aim of the trajectory analysis is to identify youth with excess adiposity, a known risk factor for cardiometabolic outcomes in adulthood

Mendelian randomization : a review of methods for the prevention, assessment, and discussion of pleiotropy in studies using the fat mass and obesity-associated gene as an instrument for adiposity

Pleiotropy assessment is critical for the validity of Mendelian randomization (MR) analyses, and its management remains a challenging task for researchers. This review examines how the authors of MR studies address bias due to pleiotropy in practice. We reviewed Pubmed, Medline, Embase and Web of Science for MR studies published before 21 May 2020 that used at least one single-nucleotide polymorphism (SNP) in the fat mass and obesity-associated (FTO) gene as instrumental variable (IV) for body mass index, irrespective of the outcome. We reviewed: 1) the approaches used to prevent pleiotropy, 2) the methods cited to detect or control the independence or the exclusion restriction assumption highlighting whether pleiotropy assessment was explicitly stated to justify the use of these methods, and 3) the discussion of findings related to pleiotropy. We included 128 studies, of which thirty-three reported one approach to prevent pleiotropy, such as the use of multiple (independent) SNPs combined in a genetic risk score as IVs. One hundred and twenty studies cited at least one method to detect or account for pleiotropy, including robust and other IV estimation methods (n = 70), methods for detection of heterogeneity between estimated causal effects across IVs (n = 72), methods to detect or account associations between IV and outcome outside thought the exposure (n = 85), and other methods (n = 5). Twenty-one studies suspected IV invalidity, of which 16 explicitly referred to pleiotropy, and six incriminating FTO SNPs. Most reviewed MR studies have cited methods to prevent or to detect or control bias due to pleiotropy. These methods are heterogeneous, their triangulation should increase the reliability of causal inference

The application of target trials with longitudinal targeted maximum likelihood estimation to assess the effect of alcohol consumption in adolescence on depressive symptoms in adulthood

Time-varying confounding is a common challenge for causal inference in observational studies with time-varying treatments, long follow-up periods, and participant dropout. Confounder adjustment using traditional approaches can also be limited by data sparsity, weight instability and computational issues. The Nicotine Dependence in Teens (NDIT) study is a prospective cohort study involving 24 data collection cycles to date, among 1,294 students recruited from 10 high schools in Montreal, Canada, including follow-up into adulthood. Our aim is to estimate associations between the timing of alcohol initiation and the cumulative duration of alcohol use on depression symptoms in adulthood. Based on the target trials framework, we define intention-to-treat and as-treated parameters in a marginal structural model with sex as a potential effect-modifier. We then use the observational data to emulate the trials. For estimation, we use pooled longitudinal target maximum likelihood estimation (LTMLE), a plug-in estimator with double robust and local efficiency properties. We describe strategies for dealing with high-dimensional potential drinking patterns and practical positivity violations due to a long follow-up time, including modifying the effect of interest by removing sparsely observed drinking patterns from the loss function and applying longitudinal modified treatment policies to represent the effect of discouraging drinking

Discrete time measures versus trajectories of drinking frequency across adolescence as predictors of binge drinking in young adulthood: a longitudinal investigation

OBJECTIVES: We compared discrete time measures with trajectories of adolescent drinking frequency as predictors of sustained binge drinking in young adulthood. DESIGN: Prospective longitudinal study. SETTING: 10 high schools in Montreal, Canada. PARTICIPANTS: 1293 high-school students followed from mean (SD) age 12 (0.6) to 24 (0.7) years. PRIMARY OUTCOME MEASURES: Patterns of drinking frequency (self-reports every 3 months from ages 12 to 17) identified using group-based trajectory modelling. Sustained binge drinking was defined as binging monthly or more often at both ages 20 and 24. ANALYSES: Using logistic regression, sustained binge drinking was regressed on trajectory group membership and on four discrete time measures (frequency of drinking at age 12; frequency of drinking at age 17; age at drinking onset; age at onset of drinking monthly or more often). RESULTS: We identified seven drinking trajectories: late triers (15.2%), decreasers (9.5%), late escalators (10.4%), early slow escalators (16.5%), steady drinkers (14.4%), early rapid escalators (15.8%) and early frequent drinkers (18.2%). Sustained binge drinking was reported by 260 of 787 participants (33.0%) with complete data at both ages 20 and 24. Decreasers did not differ from late triers; all other patterns were associated with higher odds of sustained binge drinking (adjusted ORs: AORs=1.4-17.0). All discrete time measures were associated with sustained binge drinking, notably frequency at age 12 (a bit to try and drinking monthly: (AORs=2.6 (1.7; 3.9) and 2.8 (1.3; 6.1), respectively), age of drinking onset \u3c 13 years (AOR=7.6 (3.0; 24.1)), and any age of onset of drinking monthly or more often (AORs=5.1-8.2). CONCLUSION: Youth at risk of sustained binge drinking as young adults can be identified with indicators of early drinking as early as 7th grade (aged 12-13 years). Identification of easy-to-obtain indicators can facilitate screening and intervention efforts

Associations between weight loss attempts, weight-related stress and body image during childhood and adolescence in children with parental obesity

Background: Few longitudinal studies have investigated the role of weight-loss attempts or weight-related stress on body image during childhood. We examined whether weight-loss attempts and weight-related stress are associated with weight misperception and body dissatisfaction across childhood and adolescence. Methods: Data were drawn from the Quebec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort of Canadian children with parental obesity (8–10 years: n = 630; 10–12 years: n = 564; 15–17 years: n = 377). We assessed weight-loss attempts and weight-related stress at baseline and first follow-up, and perceived and desired silhouettes at first and second follow-up with questionnaires. Weight misperception consisted of the difference in BMI z-score (zBMI) from the perceived silhouette and the measured zBMI. Body dissatisfaction consisted of the discordance between perceived and desired silhouettes. We estimated multivariable mixed-effects regression models adjusting for age, sex, pubertal stage, parental BMI and education, and sport-based teasing. Results: Weight loss attempts were associated with a higher weight misperception score (ever tried, beta [95% confidence intervals; CI]: 0.13 [0.01–0.24]) and with 2.13 times higher desire to be thinner (95% CI: 1.39–3.26) at the subsequent follow-up. Similarly, children stressed by their weight had a higher misperception score (beta [95% CI]: 0.15 [0.02–0.27]) and greater desire to be thinner at the next follow-up (odds ratio [95% CI]: 1.73 [0.999–3.00]). Conclusions: Weight-loss attempts and weight-related stress in children and adolescents are associated with weight misperception and body dissatisfaction, supporting empowerment and counseling focusing on healthy eating behaviors and a positive body image

Stable physical activity patterns predominate in a longitudinal study of physical activity among young adults in Canada from before to during the COVID-19 pandemic

We examined change in walking, moderate-to-vigorous physical activity (MVPA) and meeting MVPA guidelines from before to during the COVID-19 pandemic, and identified factors associated with newly meeting and no longer meeting MVPA guidelines during the pandemic. Complete data were available for 614 young adults participating in the ongoing Nicotine Dependence in Teens (NDIT) study pre-pandemically in 2010–12 and 2017–20, and during the pandemic in 2020–21. Change in physical activity was examined in four sub-groups (i. e., stable inactive, newly met MVPA guidelines, no longer met MVPA guidelines, stable active). Factors associated with newly and no longer met MVPA guidelines were identified in multivariable logistic regression. While walking and MVPA changed little from 2010-2 to 2017–20, both declined during the pandemic (median for both = -30 min/ week). 63.3% of participants reported no change in meeting MVPA guidelines during the pandemic, 11.4% newly met MVPA guidelines and 25.2% no longer met MVPA guidelines. Male sex, not university-educated, amotivated to engage in physical activity reported pre-pandemic, and endorsing physical activity as a COVID-19 coping strategy were associated with newly met MVPA guidelines. Male sex, not university-educated, higher problemfocused coping scores and endorsing physical activity as a COVID-19 coping strategy were protective of no longer met MVPA guidelines. Increased understanding of why some participants increased or decreased MVPA during the pandemic is needed to inform physical activity-related policy during pandemics

Genetic variants and early cigarette smoking and nicotine dependence phenotypes in adolescents

Background: While the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes. Methods: In a prospective study of 1294 adolescents aged 12–13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7–8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator). Results: The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value ,0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and selfmedication phenotypes were both 0.076. Conclusions: Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3). Impact: Dopaminergic pathways may be salient during early smoking and the development of ND

Search for cool extrasolar giant planets combining coronagraphy, spectral and angular differential imaging

Spectral differential imaging (SDI) is part of the observing strategy of current and on-going high-contrast imaging instruments on ground-based telescopes. Although it improves the star light rejection, SDI attenuates the signature of off-axis companions to the star, just like angular differential imaging (ADI). However, the attenuation due to SDI has the peculiarity of being dependent on the spectral properties of the companions. To date, no study has investigated these effects. Our team is addressing this problem based on data from a direct imaging survey of 16 stars combining the phase-mask coronagraph, the SDI and the ADI modes of VLT/NaCo. The objective of the survey is to search for cool (Teff<1000-1300 K) giant planets at separations of 5-10 AU orbiting young, nearby stars (<200 Myr, <25 pc). The data analysis did not yield any detections. As for the estimation of the sensitivity limits of SDI-processed images, we show that it requires a different analysis than that used in ADI-based surveys. Based on a method using the flux predictions of evolutionary models and avoiding the estimation of contrast, we determine directly the mass sensitivity limits of the survey for the ADI processing alone and with the combination of SDI and ADI. We show that SDI does not systematically improve the sensitivity due to the spectral properties and self-subtraction of point sources.Comment: 5 pages, 2 figure