�鶹��Ƶ

Purpose Global dietary patterns are increasingly driven by ultra-processed foods–cheap, highly palatable, and ready-to-eat options. Exploring time-related eating patterns and its association with ultra-processed foods could help in intervention efforts, but knowledge on this topic is still limited. This study assessed the association of time-related eating patterns with unprocessed/minimally processed and ultra-processed food consumption across different life stages. Methods Two 24-hour food recalls from a nationally representative sample in Brazil (Brazilian Household Budget Survey, POF, 2017–2018; n = 46,164) were used to estimate tertiles of first and last intake times, eating midpoint, caloric midpoint time, and night fasting (independent variables). All consumed foods were classified according to the Nova classification system, and the outcomes of interest were consumption of unprocessed/minimally processed and ultra-processed foods. Multiple linear regression models were performed for all individuals and stratified for each age group: adolescents (10–19 years, n = 8,469), adults (20–59 years, n = 29,332), and older individuals (≥ 60 years, n = 8,322). Results The later tertile of first food intake time, last food intake time, caloric midpoint, and eating midpoint were positively associated with consumption of ultra-processed foods (β = 3.69, 95%CI = 3.04, 4.34; β = 1.89, 95%CI = 1.32, 2.47; β = 5.20, 95%CI = 4.60, 5.81; β = 3.10, 95%CI = 2.49, 3.71, respectively) and negatively associated with consumption of unprocessed or minimally processed foods (β=-2.79, 95%CI=-3.37; -2.22; β=-1.65, 95%CI=-2.24, -1.05; β=-3.94, 95%CI=-4.44, -3.44; β=- 2.35, 95%CI=-2.93, -1.78, respectively) compared to the first “earlier” tertile (reference). An inverse association was found for night fasting (β=-1.74, 95%CI=-2.28, -1.22 and β = 1.52, 95%CI = 0.98, 2.06 for ultra-processed and unprocessed/minimally processed foods, respectively). These associations were consistent across all age groups. Conclusion Chrononutrition patterns characterized by late intake timing and shortened overnight fasting were associated with higher consumption of ultra-processed foods and lower intake of unprocessed/minimally processed foods across all age groups.

Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.

Background Greater maternal adiposity before or during pregnancy is associated with greater offspring adiposity throughout childhood, but the extent to which this is due to causal intrauterine or periconceptional mechanisms remains unclear. Here, we use Mendelian randomisation (MR) with polygenic risk scores (PRS) to investigate whether associations between maternal pre-/early pregnancy body mass index (BMI) and offspring adiposity from birth to adolescence are causal. Methods We undertook confounder adjusted multivariable (MV) regression and MR using mother-offspring pairs from two UK cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC) and Born in Bradford (BiB). In ALSPAC and BiB, the outcomes were birthweight (BW; N = 9339) and BMI at age 1 and 4 years (N = 8659 to 7575). In ALSPAC only we investigated BMI at 10 and 15 years (N = 4476 to 4112) and dual-energy X-ray absorptiometry (DXA) determined fat mass index (FMI) from age 10-18 years (N = 2659 to 3855). We compared MR results from several PRS, calculated from maternal non-transmitted alleles at between 29 and 80,939 single nucleotide polymorphisms (SNPs). Results MV and MR consistently showed a positive association between maternal BMI and BW, supporting a moderate causal effect. For adiposity at most older ages, although MV estimates indicated a strong positive association, MR estimates did not support a causal effect. For the PRS with few SNPs, MR estimates were statistically consistent with the null, but had wide confidence intervals so were often also statistically consistent with the MV estimates. In contrast, the largest PRS yielded MR estimates with narrower confidence intervals, providing strong evidence that the true causal effect on adolescent adiposity is smaller than the MV estimates (P-difference = 0.001 for 15-year BMI). This suggests that the MV estimates are affected by residual confounding, therefore do not provide an accurate indication of the causal effect size. Conclusions Our results suggest that higher maternal pre-/early-pregnancy BMI is not a key driver of higher adiposity in the next generation. Thus, they support interventions that target the whole population for reducing overweight and obesity, rather than a specific focus on women of reproductive age.

Early childhood growth patterns are associated with adult health, yet the genetic factors and the developmental stages involved are not fully understood. Here, we combine genome-wide association studies with modeling of longitudinal growth traits to study the genetics of infant and child growth, followed by functional, pathway, genetic correlation, risk score, and colocalization analyses to determine how developmental timings, molecular pathways, and genetic determinants of these traits overlap with those of adult health. We found a robust overlap between the genetics of child and adult body mass index (BMI), with variants associated with adult BMI acting as early as 4 to 6 years old. However, we demonstrated a completely distinct genetic makeup for peak BMI during infancy, influenced by variation at the LEPR/LEPROT locus. These findings suggest that different genetic factors control infant and child BMI. In light of the obesity epidemic, these findings are important to inform the timing and targets of prevention strategies.