ABSTRACT
OBJECTIVE: Genome-wide association studies have identified genetic variants associating with BMI, however, it is un-clarified whether the same variants also influence body weight fluctuations. METHODS: Among 3,982 adult individuals that attended both a baseline and a five-year follow-up examination in the Danish Inter99 intervention study, a genetic risk score (GRS) was constructed based on 30 BMI variants to address whether it is associated with body weight changes. Moreover, it was examined whether the effect of lifestyle changes was modulated by the GRS. RESULTS: The GRS associated strongly with baseline body weight, with a per risk allele increase of 0.45 (0.33-0.58) kg (P = 2.7 × 10(-12) ), corresponding to a body weight difference of 3.41 (2.21-4.60) kg comparing the highest (≥ 30 risk alleles) and lowest (≤ 26 risk alleles) risk allele tertile. No association was observed with changes in body weight during the five years. Changes in lifestyle, including physical activity, diet and smoking habits associated strongly with body weight changes, however, no interactions with the GRS was observed. CONCLUSION: The GRS associated with body weight cross-sectionally, but not with changes over a five-year period. Body weight changes were influenced by lifestyle changes, however, independently of the GRS.
Subject(s)
Body Mass Index , Body Weight/genetics , Genetic Loci , Obesity/genetics , White People/genetics , Adult , Alleles , Cross-Sectional Studies , Denmark , Diet , Follow-Up Studies , Genetic Predisposition to Disease , Genome-Wide Association Study , Genotype , Humans , Life Style , Linear Models , Middle Aged , Motor Activity , Polymorphism, Single Nucleotide , Risk Factors , Selection, GeneticABSTRACT
AIMS/HYPOTHESIS: The fetal insulin hypothesis suggests that variation in the fetal genotype influencing insulin secretion or action may predispose to low birthweight and type 2 diabetes. We examined associations between 25 confirmed type 2 diabetes risk variants and birthweight in individuals from the Danish Inter99 population and in meta-analyses including Inter99 data and reported studies. METHODS: Midwife records from the Danish State Archives provided information on mother's age and parity, as well as birthweight, length at birth and prematurity of the newborn in 4,744 individuals of the population-based Inter99 study. We genotyped 25 risk alleles showing genome-wide associations with type 2 diabetes. RESULTS: Birthweight was inversely associated with the type 2 diabetes risk alleles of ADCY5 rs11708067 (beta = -33 g [95% CI -55, -10], p = 0.004) and CDKAL1 rs7756992 (beta = -22 g [95% CI -43, -1], p = 0.04). The association for the latter locus was confirmed in a meta-analysis (n = 24,885) (beta = -20 g [95% CI -29, -11], p = 5 x 10(-6)). The HHEX-IDE rs1111875 variant showed no significant association among Danes (p = 0.09); however, in a meta-analysis (n = 25,164) this type 2 diabetes risk allele was associated with lower birthweight (beta = -16 g [95% CI -24, -8], p = 8 x 10(-5)). On average, individuals with high genetic risk (>or=25 type 2 diabetes risk alleles) weighed marginally less at birth than those with low genetic risk (<25 type 2 diabetes risk alleles) (beta = -35 g [95% CI -69, -2], p = 0.037). CONCLUSIONS/INTERPRETATION: We report a novel association between the fetal ADCY5 type 2 diabetes risk allele and decreased birthweight, and confirm in meta-analyses associations between decreased birthweight and the type 2 diabetes risk alleles of HHEX-IDE and CDKAL1. No strong general effect on birthweight can be ascribed to the 25 common type 2 diabetes risk alleles.
Subject(s)
Adenylyl Cyclases/genetics , Birth Weight/genetics , Cyclin-Dependent Kinase 5/genetics , Diabetes Mellitus, Type 2/genetics , Genome-Wide Association Study/methods , Homeodomain Proteins/genetics , Transcription Factors/genetics , Alleles , Female , Genotype , Humans , Infant, Newborn , Pregnancy , tRNA MethyltransferasesABSTRACT
Pigmented egg yolks are more attractive. Popular culture treats annatto as a powerful anticholesterolemic agent, besides being widely used in the form of industry pigment. This work evaluated the effects of the addition of annatto (Bixa orellana L.) in the feed of hens, verifying a possible alteration of cholesterol in the yolks, content of carotenes, and iron and available iron, over time. One hundred and twenty-five hens divided in control (0% - T1) and four annatto-added treatments (0.5% - T2; 1.0% - T3; 1.5% - T4, and 2.0% - T5) were used. Eggs were collected at 23, 25, 27, 29 and 30 weeks. The animals were randomly separated into five groups of five animals each. The cholesterol was measured by the colorimetric method, vitamin A (ß and α carotene) by spectrophotometry, total iron by atomic absorption spectrophotometry, and dialysable iron by dialysis. Tukey's test was used at the 5% level for comparison of the averages. Regarding cholesterol, treatments T2 and T3 did not differ significantly. However, other treatments differed ( P ≤ 0.05) from the control, decreasing the cholesterol level as the percentage of annatto in the feed increased. In time, there was a significant increase ( P ≤ 0.05). For ß and α carotene, T5 presented statistically higher values than the others ( P ≤ 0.05). With regard to total iron, T5 had higher values than the others. Dialysable iron was also higher, probably due to the increase in carotenes. Thus, we can conclude that the use of annatto in the feed of layer hens is useful, as it provokes the reduction of cholesterol and promotes an increase in the content of iron and carotenes in eggs.
