Sugar-sweetened beverage consumption may modify associations between genetic variants in the CHREBP (carbohydrate responsive element binding protein) locus and HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations

BACKGROUND: ChREBP (carbohydrate responsive element binding protein) is a transcription factor that responds to sugar consumption. Sugar-sweetened beverage (SSB) consumption and genetic variants in the CHREBP locus have separately been linked to HDL-C (high-density lipoprotein cholesterol) and triglyceride concentrations. We hypothesized that SSB consumption would modify the association between genetic variants in the CHREBP locus and dyslipidemia.METHODS: Data from 11 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (N=63599) and the UK Biobank (N=59220) were used to quantify associations of SSB consumption, genetic variants, and their interaction on HDL-C and triglyceride concentrations using linear regression models. A total of 1606 single nucleotide polymorphisms within or near CHREBP were considered. SSB consumption was estimated from validated questionnaires, and participants were grouped by their estimated intake.RESULTS: In a meta-analysis, rs71556729 was significantly associated with higher HDL-C concentrations only among the highest SSB consumers (beta, 2.12 [95% CI, 1.16-3.07] mg/dL per allele; P<0.0001), but not significantly among the lowest SSB consumers (P=0.81; P-Diff<0.0001). Similar results were observed for 2 additional variants (rs35709627 and rs71556736). For triglyceride, rs55673514 was positively associated with triglyceride concentrations only among the highest SSB consumers (beta, 0.06 [95% CI, 0.02-0.09] In-mg/dL per allele, P=0.001) but not the lowest SSB consumers (P=0.84; P-Diff=0.0005).CONCLUSIONS: Our results identified genetic variants in the CHREBP locus that may protect against SSB-associated reductions in HDL-C and other variants that may exacerbate SSB-associated increases in triglyceride concentrations.Clinical epidemiolog

Associations of autozygosity with a broad range of human phenotypes

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding

Avaliação de dois simuladores para predição da lixiviação de sulfona de aldicarbe em um Latossolo Vermelho-Amarelo Evaluation of two simulators to predict the leaching of aldoxycarb in a red-yellow latossol

Este trabalho teve por objetivo o estudo da lixiviação de sulfona de aldicarbe em um Latossolo Vermelho-Amarelo, na região de Lavras, MG, para posterior comparação com os resultados obtidos pelos simuladores CALF e PESTLA. Os resultados mostraram alta lixiviação de sulfona de aldicarbe no solo em estudo. Aos 44 dias após a aplicação do inseticida e com uma lâmina de água acumulada de 241,4 mm, a quantidade média de sulfona de aldicarbe remanescente nas colunas de solo de 45 cm de profundidade foi equivalente a 17,92% (±5,88) da dose aplicada, enquanto os simuladores CALF e PESTLA estimaram 20,52% e 37,82%, respectivamente. O simulador CALF gerou melhores estimativas da quantidade média de sulfona de aldicarbe no perfil do solo nas diferentes datas de amostragem, enquanto o simulador PESTLA gerou melhores estimativas da distribuição do inseticida ao longo do perfil do solo, nas diferentes datas de amostragem.<br>This work was carried out to study the leaching of aldoxycarb in a Red Yellow Latossol in Lavras, Minas Gerais State, Brazil, and to compare the observed results with those obtained by the simulators CALF and PESTLA. The results showed a high leaching of aldoxycarb in the soil. After 44 days of the insecticide application and with 241.4 mm of accumulated water applied in each column, the remained quantity of aldoxycarb in the soil columns (45 cm long) was 17.92% (±5.88) of the initial applied rate. However, the simulators CALF and PESTLA predicted 20.52% and 37.82%, respectively. CALF simulator gave better predictions of the overall mean residue concentrations of aldoxycarb, and PESTLA simulator gave better prediction of residues distribution

Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.

Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10 &lt;sup&gt;-16&lt;/sup&gt; , n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity