The effect of communicating the genetic risk of cardiometabolic disorders on motivation and actual engagement in preventative lifestyle modification and clinical outcome: a systematic review and meta-analysis of randomised controlled trials.

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.Medical Research CouncilThis is the final version of the article. It first appeared from Cambridge University Press via https://doi.org/10.1017/S0007114516002488

Genome-wide meta-analysis of macronutrient intake of 91,114 European ancestry participants from the cohorts for heart and aging research in genomic epidemiology consortium

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 \u3c 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

Prospective Evaluation over 15 Years of Six Breast Cancer Risk Models.

Prospective validation of risk models is needed to assess their clinical utility, particularly over the longer term. We evaluated the performance of six commonly used breast cancer risk models (IBIS, BOADICEA, BRCAPRO, BRCAPRO-BCRAT, BCRAT, and iCARE-lit). 15-year risk scores were estimated using lifestyle factors and family history measures from 7608 women in the Melbourne Collaborative Cohort Study who were aged 50-65 years and unaffected at commencement of follow-up two (conducted in 2003-2007), of whom 351 subsequently developed breast cancer. Risk discrimination was assessed using the C-statistic and calibration using the expected/observed number of incident cases across the spectrum of risk by age group (50-54, 55-59, 60-65 years) and family history of breast cancer. C-statistics were higher for BOADICEA (0.59, 95% confidence interval (CI) 0.56-0.62) and IBIS (0.57, 95% CI 0.54-0.61) than the other models (p-difference ≤ 0.04). No model except BOADICEA calibrated well across the spectrum of 15-year risk (p-value < 0.03). The performance of BOADICEA and IBIS was similar across age groups and for women with or without a family history. For middle-aged Australian women, BOADICEA and IBIS had the highest discriminatory accuracy of the six risk models, but apart from BOADICEA, no model was well-calibrated across the risk spectrum.This work was primarily supported by grant 1129136 from the Australian National Health and Medical Research Council (NHMRC) (https://www.nhmrc.gov.au/). MCCS cohort recruitment was funded by Cancer Council Victoria (https://www.cancervic.org.au/) and VicHealth (https://www.vichealth.vic.gov.au/). The MCCS was further supported by Australian NHMRC grants 209057, 396414 and 1074383, and ongoing follow-up and data management has been funded by Cancer Council Victoria since 1995. Cases and their vital status were ascertained through the Victorian Cancer Registry and the Australian Institute of Health and Welfare, including the National Death Index and the Australian Cancer Database.TN-D is a recipient of a Career Development Fellowship from the National Breast Cancer Foundation (Australia). JLH and MCS are Senior Principal and Senior Research Fellows of the National Health and Medical Research Council (Australia), respectively. ACA and AJL are supported by grants from Cancer Research UK (C12292/A20861 and PPRPGM19 Nov20\100002)

Association of Markers of Inflammation, the Kynurenine Pathway and B Vitamins with Age and Mortality, and a Signature of Inflammaging

Under embargo until: 2022-06-12Background Inflammation is a key feature of aging. We aimed to (i) investigate the association of 34 blood markers potentially involved in inflammatory processes with age and mortality and (ii) develop a signature of “inflammaging.” Methods Thirty-four blood markers relating to inflammation, B vitamin status, and the kynurenine pathway were measured in 976 participants in the Melbourne Collaborative Cohort Study at baseline (median age = 59 years) and follow-up (median age = 70 years). Associations with age and mortality were assessed using linear and Cox regression, respectively. A parsimonious signature of inflammaging was developed and its association with mortality was compared with 2 marker scores calculated across all markers associated with age and mortality, respectively. Results The majority of markers (30/34) were associated with age, with stronger associations observed for neopterin, cystatin C, interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), several markers of the kynurenine pathway and derived indices KTR (kynurenine/tryptophan ratio), PAr index (ratio of 4-pyridoxic acid and the sum of pyridoxal 5′-phosphate and pyridoxal), and HK:XA (3-hydroxykynurenine/xanthurenic acid ratio). Many markers (17/34) showed an association with mortality, in particular IL-6, neopterin, C-reactive protein, quinolinic acid, PAr index, and KTR. The inflammaging signature included 10 markers and was strongly associated with mortality (hazard ratio [HR] per SD = 1.40, 95% CI: 1.24–1.57, p = 2 × 10−8), similar to scores based on all age-associated (HR = 1.38, 95% CI: 1.23–1.55, p = 4 × 10−8) and mortality-associated markers (HR = 1.43, 95% CI: 1.28–1.60, p = 1 × 10−10), respectively. Strong evidence of replication of the inflammaging signature association with mortality was found in the Hordaland Health Study. Conclusion Our study highlights the key role of the kynurenine pathway and vitamin B6 catabolism in aging, along with other well-established inflammation-related markers. A signature of inflammaging based on 10 markers was strongly associated with mortality.acceptedVersio

Interplay between genetic predisposition, macronutrient intake and type 2 diabetes incidence: analysis within EPIC-InterAct across eight European countries.

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

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

The effect of communicating genetic risk of cardiometabolic disorders on motivation and actual engagement in preventative lifestyle modification and clinical outcome:A systematic review and meta-analysis of randomised controlled trials

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) -015; 95 % CI -103, 073, P=074) or actual change in dietary behaviour. Similar results were observed for actual weight loss (control v. high genetic risk SMD 029 kg; 95 % CI -074, 131, P=058). 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

The application of genetics and nutritional genomics in practice:an international survey of knowledge, involvement and confidence among dietitians in the US, Australia and the UK

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 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

A preliminary qualitative exploration of dietitians' engagement with genetics and nutritional genomics: perspectives from international leaders

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