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Mol Psychiatry ; 2018 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-29988085


Macronutrient intake, the proportion of calories consumed from carbohydrate, fat, and protein, is an important risk factor for metabolic diseases with significant familial aggregation. Previous studies have identified two genetic loci for macronutrient intake, but incomplete coverage of genetic variation and modest sample sizes have hindered the discovery of additional loci. Here, we expanded the genetic landscape of macronutrient intake, identifying 12 suggestively significant loci (P < 1 × 10-6) associated with intake of any macronutrient in 91,114 European ancestry participants. Four loci replicated and reached genome-wide significance in a combined meta-analysis including 123,659 European descent participants, unraveling two novel loci; a common variant in RARB locus for carbohydrate intake and a rare variant in DRAM1 locus for protein intake, and corroborating earlier FGF21 and FTO findings. In additional analysis of 144,770 participants from the UK Biobank, all identified associations from the two-stage analysis were confirmed except for DRAM1. Identified loci might have implications in brain and adipose tissue biology and have clinical impact in obesity-related phenotypes. Our findings provide new insight into biological functions related to macronutrient intake.

Diabetologia ; 61(6): 1325-1332, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29549418


AIMS/HYPOTHESIS: Gene-macronutrient interactions may contribute to the development of type 2 diabetes but research evidence to date is inconclusive. We aimed to increase our understanding of the aetiology of type 2 diabetes by investigating potential interactions between genes and macronutrient intake and their association with the incidence of type 2 diabetes. METHODS: We investigated the influence of interactions between genetic risk scores (GRSs) for type 2 diabetes, insulin resistance and BMI and macronutrient intake on the development of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct, a prospective case-cohort study across eight European countries (N = 21,900 with 9742 incident type 2 diabetes cases). Macronutrient intake was estimated from diets reported in questionnaires, including proportion of energy derived from total carbohydrate, protein, fat, plant and animal protein, saturated, monounsaturated and polyunsaturated fat and dietary fibre. Using multivariable-adjusted Cox regression, we estimated country-specific interaction results on the multiplicative scale, using random-effects meta-analysis. Secondary analysis used isocaloric macronutrient substitution. RESULTS: No interactions were identified between any of the three GRSs and any macronutrient intake, with low-to-moderate heterogeneity between countries (I2 range 0-51.6%). Results were similar using isocaloric macronutrient substitution analyses and when weighted and unweighted GRSs and individual SNPs were examined. CONCLUSIONS/INTERPRETATION: Genetic susceptibility to type 2 diabetes, insulin resistance and BMI did not modify the association between macronutrient intake and incident type 2 diabetes. This suggests that macronutrient intake recommendations to prevent type 2 diabetes do not need to account for differences in genetic predisposition to these three metabolic conditions.

Am J Clin Nutr ; 106(1): 263-275, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28592605


Background: Gene-diet interactions have been reported to contribute to the development of type 2 diabetes (T2D). However, to our knowledge, few examples have been consistently replicated to date.Objective: We aimed to identify existing evidence for gene-macronutrient interactions and T2D and to examine the reported interactions in a large-scale study.Design: We systematically reviewed studies reporting gene-macronutrient interactions and T2D. We searched the MEDLINE, Human Genome Epidemiology Network, and WHO International Clinical Trials Registry Platform electronic databases to identify studies published up to October 2015. Eligibility criteria included assessment of macronutrient quantity (e.g., total carbohydrate) or indicators of quality (e.g., dietary fiber) by use of self-report or objective biomarkers of intake. Interactions identified in the review were subsequently examined in the EPIC (European Prospective Investigation into Cancer)-InterAct case-cohort study (n = 21,148, with 9403 T2D cases; 8 European countries). Prentice-weighted Cox regression was used to estimate country-specific HRs, 95% CIs, and P-interaction values, which were then pooled by random-effects meta-analysis. A primary model was fitted by using the same covariates as reported in the published studies, and a second model adjusted for additional covariates and estimated the effects of isocaloric macronutrient substitution.Results: Thirteen observational studies met the eligibility criteria (n < 1700 cases). Eight unique interactions were reported to be significant between macronutrients [carbohydrate, fat, saturated fat, dietary fiber, and glycemic load derived from self-report of dietary intake and circulating n-3 (ω-3) polyunsaturated fatty acids] and genetic variants in or near transcription factor 7-like 2 (TCF7L2), gastric inhibitory polypeptide receptor (GIPR), caveolin 2 (CAV2), and peptidase D (PEPD) (P-interaction < 0.05). We found no evidence of interaction when we tried to replicate previously reported interactions. In addition, no interactions were detected in models with additional covariates.Conclusions: Eight gene-macronutrient interactions were identified for the risk of T2D from the literature. These interactions were not replicated in the EPIC-InterAct study, which mirrored the analyses undertaken in the original reports. Our findings highlight the importance of independent replication of reported interactions.

Diabetes Mellitus/etiologia , Dieta , Carboidratos da Dieta/farmacologia , Gorduras na Dieta/farmacologia , Fibras na Dieta/farmacologia , Comportamento Alimentar , Interação Gene-Ambiente , Estudos de Casos e Controles , Caveolina 2/genética , Diabetes Mellitus/genética , Dipeptidases/genética , Ingestão de Energia , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Receptores dos Hormônios Gastrointestinais/genética , Fatores de Risco , Proteína 2 Semelhante ao Fator 7 de Transcrição/genética
Br J Nutr ; 116(5): 924-34, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27405704


Genetic risk prediction of chronic conditions including obesity, diabetes and CVD currently has limited predictive power but its potential to engage healthy behaviour change has been of immense research interest. We aimed to understand whether the latter is indeed true by conducting a systematic review and meta-analysis investigating whether genetic risk communication affects motivation and actual behaviour change towards preventative lifestyle modification. We included all randomised controlled trials (RCT) since 2003 investigating the impact of genetic risk communication on health behaviour to prevent cardiometabolic disease, without restrictions on age, duration of intervention or language. We conducted random-effects meta-analyses for perceived motivation for behaviour change and clinical changes (weight loss) and a narrative analysis for other outcomes. Within the thirteen studies reviewed, five were vignette studies (hypothetical RCT) and seven were clinical RCT. There was no consistent effect of genetic risk on actual motivation for weight loss, perceived motivation for dietary change (control v. genetic risk group standardised mean difference (smd) -0·15; 95 % CI -1·03, 0·73, P=0·74) or actual change in dietary behaviour. Similar results were observed for actual weight loss (control v. high genetic risk SMD 0·29 kg; 95 % CI -0·74, 1·31, P=0·58). This review found no clear or consistent evidence that genetic risk communication alone either raises motivation or translates into actual change in dietary intake or physical activity to reduce the risk of cardiometabolic disorders in adults. Of thirteen studies, eight were at high or unclear risk of bias. Additional larger-scale, high-quality clinical RCT are warranted.

Doenças Cardiovasculares/genética , Diabetes Mellitus Tipo 2/genética , Obesidade/genética , Doenças Cardiovasculares/etiologia , Humanos , Fatores de Risco
J Allied Health ; 43(4): 221-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25433186


UNLABELLED: This qualitative study explored the underlying determinants of dietitians' current practice and attitudes about nutritional genomics. METHODS: Sixteen semi-structured interviews were conducted with international leaders selected across each domain of dietetics practice from Australia (n=8) and the United Kingdom (n=8). Interviews explored knowledge, involvement, perceived role, and attitudes about the benefits and barriers of genetics and nutritional genomics. Interviews were transcribed and analysed using thematic analysis. RESULTS: Five key themes were identified: (i) acknowledgment that there are wide applications for nutritional genomics; (ii) a general lack of awareness of nutritional genomics that underlies a knowledge, skills, and confidence gap; (iii) dietitians are patient-orientated and thus are receptive to the public's needs; (iv) the legitimacy of commercialised nutritional genomics products and services; and (v) prioritisation of nutritional genomics amongst other practice-related commitments as well as the influence of the workplace setting. CONCLUSIONS: In order for healthcare services to prepare for the application of nutritional genomics, these social, political, attitudinal, and awareness issues amongst dietitians need to be addressed. Further education in nutritional genomics may help to build awareness, continued research is crucial in determining utility, whilst establishing a healthcare system that supports and rewards this approach may cultivate its adoption.

Conhecimentos, Atitudes e Prática em Saúde , Nutrigenômica/métodos , Nutricionistas/psicologia , Conscientização , Humanos , Entrevistas como Assunto , Liderança , Política , Papel Profissional , Pesquisa Qualitativa
Genes Nutr ; 8(6): 523-33, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23861045


As a result of expanding scientific understanding of the interplay between genetics and dietary risk factors, those involved in nutritional management need to understand genetics and nutritional genomics in order to inform management of individuals and groups. The aim of this study was to measure and determine factors affecting dietitians' knowledge, involvement and confidence in genetics and nutritional genomics across the US, Australia and the UK. A cross-sectional study was undertaken using an online questionnaire that measured knowledge and current involvement and confidence in genetics and nutritional genomics. The questionnaire was distributed to dietitians in the US, Australia and the UK using email lists from the relevant professional associations. Data were collected from 1,844 dietitians who had practiced in the previous 6 months. The main outcomes were knowledge of genetics and nutritional genomics and involvement and confidence in undertaking clinical and educational activities related to genetics and nutritional genomics. Mean scores for knowledge, involvement and confidence were calculated. Analysis of variance and χ (2) analysis were used to compare scores and frequencies. Multivariate linear regression was used to determine predictors of high scores. The results demonstrated significant differences in involvement (p < 0.001) and confidence (p < 0.001) but not knowledge scores (p = 0.119) between countries. Overall, dietitians reported low levels of knowledge (mean knowledge score 56.3 %), involvement (mean number of activities undertaken 20.0-22.7 %) and confidence (mean confidence score 25.8-29.7 %). Significant relationships between confidence, involvement and knowledge were observed. Variables relating to education, experience, sector of employment and attitudes were also significantly associated with knowledge, involvement and confidence. Dietitians' knowledge, involvement and confidence relating to genetics and nutritional genomics remain low and further investigation into factors contributing to this is required.