The association between cognitive ability and body mass index: A sibling-comparison analysis in four longitudinal studies

BACKGROUND: Body mass index (BMI) and obesity rates have increased sharply since the 1980s. While multiple epidemiologic studies have found that higher adolescent cognitive ability is associated with lower adult BMI, residual and unobserved confounding due to family background may explain these associations. We used a sibling design to test this association accounting for confounding factors shared within households. METHODS AND FINDINGS: We used data from four United States general youth population cohort studies: the National Longitudinal Study of Youth 1979 (NLSY-79), the NLSY-79 Children and Young Adult, the NLSY 1997 (NLSY-97), and the Wisconsin Longitudinal Study (WLS); a total of 12,250 siblings from 5,602 households followed from adolescence up to age 62. We used random effects within-between (REWB) and residualized quantile regression (RQR) models to compare between- and within-family estimates of the association between adolescent cognitive ability and adult BMI (20 to 64 years). In REWB models, moving from the 25th to 75th percentile of adolescent cognitive ability was associated with -0.95 kg/m2 (95% CI = -1.21, -0.69) lower BMI between families. Adjusting for family socioeconomic position reduced the association to -0.61 kg/m2 (-0.90, -0.33). However, within families, the association was just -0.06 kg/m2 (-0.35, 0.23). This pattern of results was found across multiple specifications, including analyses conducted in separate cohorts, models examining age-differences in association, and in RQR models examining the association across the distribution of BMI. Limitations include the possibility that within-family estimates are biased due to measurement error of the exposure, confounding via non-shared factors, and carryover effects. CONCLUSIONS: The association between high adolescent cognitive ability and low adult BMI was substantially smaller in within-family compared with between-family analysis. The well-replicated associations between cognitive ability and subsequent BMI may largely reflect confounding by family background factors

Determinants of the population health distribution: an illustration examining body mass index

Most epidemiological studies examine how risk factors relate to average difference in outcomes (linear regression) or odds of a binary outcome (logistic regression); they do not explicitly examine whether risk factors are associated differentially across the distribution of the health outcome investigated. This paper documents a phenomenon found repeatedly in the minority of epidemiological studies which do this (via quantile regression); associations between a range of established risk factors and body mass index (BMI) are progressively stronger in the upper ends of the BMI distribution. In this paper, we document this finding and provide illustrative evidence of it in the 1958 British birth cohort study. Associations of low childhood socioeconomic position, high maternal weight, low childhood general cognition and adult physical inactivity with higher BMI are larger at the upper end of the BMI distribution, on both absolute and relative scales. For example, effect estimates for socioeconomic position and childhood cognition were around three times larger at the 90th compared with 10th quantile, while effect estimates for physical inactivity were increasingly larger from the 50th-90th quantiles, yet null at lower quantiles. We provide potential explanations for these findings and discuss implications. Risk factors may have larger causal effects amongst those in worse health, and these effects may not be discovered when health is only examined in average terms. In such scenarios, population-based approaches to intervention may have larger benefits than anticipated when assuming equivalent benefit across the population.. Further research is needed to understand why effect estimates differ across the BMI outcome distribution and investigate whether differential effects exist for other physical and mental health outcomes

Infant weight gain and adolescent body mass index: comparison across two British cohorts born in 1946 and 2001

Objective To investigate how the relationship of infant weight gain with adolescent body mass index (BMI) differs for individuals born during compared to before the obesity epidemic era. Design Data from two British birth cohorts, the 1946 National Survey of Health and Development (NSHD, n = 4,199) and the 2001 Millennium Cohort Study (MCS, n = 9,417), were used to estimate and compare associations of infant weight gain between ages 0-3 years with adolescent outcomes. Main outcome measures BMI Z-scores and overweight/ obesity at ages 11 and 14 years. Results Infant weight gain, in Z-scores, was positively associated with adolescent BMI Z-scores in both cohorts. Non-linearity in the MCS meant that associations were only stronger than in the NSHD when infant weight gain was above -1 Z-score. Using decomposition analysis, between-cohort differences in association accounted for 20-30% of the differences (secular increases) in BMI Z-scores, although the underlying estimates were not precise with 95% confidence intervals (CI) crossing zero. Conversely, between-cohort differences in the distribution of infant weight gain accounted for approximately 9% of the differences (secular increases) in BMI Z-scores, and the underlying estimates were precise with 95% CI not crossing zero. Relative to normal weight gain (change of -0.67 to +0.67 Z-scores between ages 0-3 years), very rapid infant weight gain (> 1.34), but not rapid weight gain (+0.67 to +1.34), was associated with higher BMI Z-scores more strongly in the MCS (β = 0.790; 95% CI = 0.717, 0.862 at age 11 years) than the NSHD (0.573; 0.466, 0.681); p < 0.001 for between-cohort difference. The relationship of slow infant weight gain (< -0.67) with lower adolescent BMI was also stronger in the MCS. Very rapid or slow infant weight gain were not, however, more strongly associated with increased risk of adolescent overweight/ obesity or thinness, respectively, in the more recently born cohort. Conclusions Greater infant weight gain, at the middle/ upper-end of the distribution, was more strongly associated with higher adolescent BMI among individuals born during (compared to before) the obesity epidemic. Combined with a secular change toward greater infant weight gain, these results suggest that there are likely to be associated negative consequences for population-level health and wellbeing in the future, unless effective interventions are developed and implemented

Weakening of the cognition and height association from 1957 to 2018: Findings from four British birth cohort studies

BACKGROUND: Taller individuals have been repeatedly found to have higher scores on cognitive assessments. Recent studies have suggested that this association can be explained by genetic factors, yet this does not preclude the influence of environmental or social factors that may change over time. We thus tested whether the association changed across time using data from four British birth cohorts (born in 1946, 1958, 1970, and 2001). METHODS: In each cohort height was measured and cognition via verbal reasoning, vocabulary/comprehension, and mathematical tests; at ages 10/11 and 14/17 years (N=41,418). We examined associations between height and cognition at each age, separately in each cohort, and for each cognitive test administered. Linear and quantile regression models were used. RESULTS: Taller participants had higher mean cognitive assessment scores in childhood and adolescence, yet the associations were weaker in later (1970 and 2001) cohorts. For example, the mean difference in height comparing the highest with lowest verbal cognition scores at 10/11 years was 0.57 SD (95% CI = 0.44-0.70) in the 1946 cohort, yet 0.30 SD (0.23-0.37) in the 2001 cohort. Expressed alternatively, there was a reduction in correlation from 0.17 (0.15-0.20) to 0.08 (0.06-0.10). This pattern of change in the association was observed across all ages and cognition measures used, was robust to adjustment for social class and parental height, and modeling of plausible missing-not-at-random scenarios. Quantile regression analyses suggested that these differences were driven by differences in the lower centiles of height, where environmental influence may be greatest. CONCLUSIONS: Associations between height and cognitive assessment scores in childhood-adolescence substantially weakened from 1957-2018. These results support the notion that environmental and social change can markedly weaken associations between cognition and other traits. FUNDING: DB is supported by the Economic and Social Research Council (grant number ES/M001660/1); DB and LW by the Medical Research Council (MR/V002147/1). The Medical Research Council (MRC) and the University of Bristol support the MRC Integrative Epidemiology Unit [MC_UU_00011/1]. NMD is supported by an Norwegian Research Council Grant number 295989. VM is supported by the CLOSER Innovation Fund WP19 which is funded by the Economic and Social Research Council (award reference: ES/K000357/1) and Economic and Social Research Council (ES/M001660/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Association of childhood psychomotor coordination with survival up to 6 decades later

Importance: Poorer performance on standard tests of motor coordination in children has emerging links with sedentary behavior, obesity, and functional capacity in later life. These observations are suggestive of an untested association of coordination with health outcomes, including mortality. Objective: To examine the association of performance on a series of psychomotor coordination tests in childhood with mortality up to 6 decades later. Design, Setting, and Participants: The British National Child Development Study (1958 Birth Cohort Study) is a prospective cohort study based on a nationally representative sample of births from England, Scotland, and Wales. A total of 17 415 individuals had their gross and fine motor psychomotor coordination assessed using 9 tests at ages 11 and 16 years. Data analysis for the present study was conducted from October 2016 to December 2019. Main Outcomes and Measures: All-cause mortality as ascertained from a vital status registry and survey records. Results: In this birth cohort study of 17 415 individuals who underwent a series of psychomotor coordination tests in childhood, follow up was conducted over several decades. Of the analytical sample of 12 678 individuals, 51% were male, and 72% came from a lower social group. Mortality surveillance between ages 12 and 58 years in an analytical sample of 17 062 men and women yielded 1072 deaths (766 661 person-years at risk). In survival analyses with adjustment for sex, higher scores on 7 of the 9 childhood coordination tests were associated with a lower risk of mortality in a stepwise manner. After controlling for early-life socioeconomic, health, cognitive, and developmental factors, lower mortality was statistically significantly associated with 3 tests: ball catching at age 11 years (0-8 vs 10 catches: hazard ratio [HR], 1.57; 95% CI, 1.19-2.07), match-picking at age 11 years (>50 vs 0-36 seconds: HR, 1.33; 95% CI, 1.09-1.63), and hopping at age 16 years (very unsteady vs very steady: HR, 1.28; 95% CI, 1.01-1.63). Conclusions and Relevance: The results of this cohort study suggest that childhood motor coordination is associated with lower mortality up to middle-age; these findings require replication

Polygenic and socioeconomic risk for high body mass index:69 years of follow-up across life

Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2-69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2-69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, the trajectories of effect size (β) and explained variance (R2) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; quantile regression analyses showed that effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance ('non-shared') environmental influences on BMI across life

2-Fluoro-l-histidine

The title compound, C6H8FN3O2, an analog of histidine, shows a reduced side-chain pKa (ca 1). The title structure exhibits a shortening of the bond between the proximal ring N atom and the F-substituted ring C atom, indicating an increase in π-bond character due to an inductive effect of fluorine

Socioeconomic inequalities in childhood-to-adulthood BMI tracking in three British birth cohorts

Background: Body mass index (BMI) tracks from childhood to adulthood, but the extent to which this relationship varies across the distribution and according to socio-economic position (SEP) is unknown. We aimed to address this using data from three British cohort studies. Methods: We used data from: 1946 National Survey of Health and Development (NSHD, n=2,470); 1958 National Child Development Study (NCDS, n=7,747); 1970 British Cohort Study (BCS, n=5,323). BMI tracking between 11 and 42 years was estimated using quantile regression, with estimates reflecting correlation coefficients. SEP disparities in tracking were investigated using a derived SEP variable based on parental education reported in childhood. This SEP variable was then interacted with the 11-year BMI z-score. Results: In each cohort and sex, tracking was stronger at the upper end of the distribution of BMI at 42 years. For example, for men in the 1946 NSHD, the tracking estimate at the 10th quantile was 0.31 (0.20, 0.41), increasing to 0.71 (0.61, 0.82) at the 90th quantile. We observed no strong evidence of SEP inequalities in tracking in men in the 1946 and 1958 cohorts. In the 1970 cohort, however, we observed tentative evidence of stronger tracking in low SEP groups, particularly in women and at the higher end of the BMI distribution. For example, women in the 1970 cohort from low SEP backgrounds had tracking coefficients at the 50th, 70th, and 90th quantiles which were 0.05 (-0.04; 0.15), 0.19 (0.06; 0.31), and 0.22 (0.02; 0.43) units higher, respectively, than children from high SEP groups. Conclusion: Tracking was consistently stronger at the higher quantiles of the BMI distribution. We observed suggestive evidence for a pattern of greater BMI tracking in lower (compared to higher) SEP groups in the more recently born cohort, particularly in women and at the higher end of the BMI distribution