| 1. |
- Atabaki-Pasdar, Naeimeh, et al.
(författare)
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Statistical power considerations in genotype-based recall randomized controlled trials
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Randomized controlled trials (RCT) are often underpowered for validating gene-treatment interactions. Using published data from the Diabetes Prevention Program (DPP), we examined power in conventional and genotype-based recall (GBR) trials. We calculated sample size and statistical power for gene-metformin interactions (vs. placebo) using incidence rates, gene-drug interaction effect estimates and allele frequencies reported in the DPP for the rs8065082 SLC47A1 variant, a metformin transported encoding locus. We then calculated statistical power for interactions between genetic risk scores (GRS), metformin treatment and intensive lifestyle intervention (ILI) given a range of sampling frames, clinical trial sample sizes, interaction effect estimates, and allele frequencies; outcomes were type 2 diabetes incidence (time-to-event) and change in small LDL particles (continuous outcome). Thereafter, we compared two recruitment frameworks: GBR (participants recruited from the extremes of a GRS distribution) and conventional sampling (participants recruited without explicit emphasis on genetic characteristics). We further examined the influence of outcome measurement error on statistical power. Under most simulated scenarios, GBR trials have substantially higher power to observe gene-drug and gene-lifestyle interactions than same-sized conventional RCTs. GBR trials are becoming popular for validation of gene-treatment interactions; our analyses illustrate the strengths and weaknesses of this design.
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| 2. |
- Chen, Yan, et al.
(författare)
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The combined effects of FADS gene variation and dietary fats in obesity-related traits in a population from the far north of Sweden : the GLACIER Study
- 2019
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 43:4, s. 808-820
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Tidskriftsartikel (refereegranskat)abstract
- Background: Recent analyses in Greenlandic Inuit identified six genetic polymorphisms (rs74771917, rs3168072, rs12577276, rs7115739, rs174602 and rs174570) in the fatty acid desaturase gene cluster (FADS1-FADS2-FADS3) that are associated with multiple metabolic and anthropometric traits. Our objectives were to systematically assess whether dietary polyunsaturated fatty acid (PUFA) intake modifies the associations between genetic variants in the FADS gene cluster and cardiometabolic traits, and to functionally annotate top-ranking candidates to estimate their regulatory potential. Methods: Data analyses consisted of the following: interaction analyses between the 6 candidate genetic variants and dietary PUFA intake; gene-centric joint analyses to detect interaction signals in the FADS region; haplotype-centric joint tests across 30 haplotype blocks in the FADS region to refine interaction signals; and functional annotation of top-ranking loci from the previous steps. These analyses were undertaken in Swedish adults from the GLACIER Study (N = 5,160); data on genetic variation and eight cardiometabolic traits were used. Results: Interactions were observed between rs174570 and n-6 PUFA intake on fasting glucose (Pint = 0.005) and between rs174602 and n-3 PUFA intake on total cholesterol (Pint = 0.001). Gene-centric analyses demonstrated a statistically significant interaction effect for FADS and n-3 PUFA on triglycerides (Pint = 0.005) considering genetic main effects as random. Haplotype analyses revealed three blocks (Pint < 0.011) that could drive the interaction between FADS and n-3 PUFA on triglycerides; functional annotation of these regions showed that each block harbours a number of highly functional regulatory variants; FADS2 rs5792235 demonstrated the highest functionality score. Conclusions: The association between FADS variants and triglycerides may be modified by PUFA intake. The intronic FADS2 rs5792235 variant is a potential causal variant in the region, having the highest regulatory potential. However, our results suggest that multiple haplotypes may harbour functional variants in a region, rather than a single causal variant.
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| 3. |
- Koivula, Robert W., et al.
(författare)
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Discovery of biomarkers for glycaemic deterioration before and after the onset of type 2 diabetes : descriptive characteristics of the epidemiological studies within the IMI DIRECT Consortium
- 2019
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 62:9, s. 1601-1615
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Here, we describe the characteristics of the Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) epidemiological cohorts at baseline and follow-up examinations (18, 36 and 48 months of follow-up).Methods: From a sampling frame of 24,682 adults of European ancestry enrolled in population-based cohorts across Europe, participants at varying risk of glycaemic deterioration were identified using a risk prediction algorithm (based on age, BMI, waist circumference, use of antihypertensive medication, smoking status and parental history of type 2 diabetes) and enrolled into a prospective cohort study (n = 2127) (cohort 1, prediabetes risk). We also recruited people from clinical registries with type 2 diabetes diagnosed 6-24 months previously (n = 789) into a second cohort study (cohort 2, diabetes). Follow-up examinations took place at similar to 18 months (both cohorts) and at similar to 48 months (cohort 1) or similar to 36 months (cohort 2) after baseline examinations. The cohorts were studied in parallel using matched protocols across seven clinical centres in northern Europe.Results: Using ADA 2011 glycaemic categories, 33% (n = 693) of cohort 1 (prediabetes risk) had normal glucose regulation and 67% (n = 1419) had impaired glucose regulation. Seventy-six per cent of participants in cohort 1 was male. Cohort 1 participants had the following characteristics (mean +/- SD) at baseline: age 62 (6.2) years; BMI 27.9 (4.0) kg/m(2); fasting glucose 5.7 (0.6) mmol/l; 2 h glucose 5.9 (1.6) mmol/l. At the final follow-up examination the participants' clinical characteristics were as follows: fasting glucose 6.0 (0.6) mmol/l; 2 h OGTT glucose 6.5 (2.0) mmol/l. In cohort 2 (diabetes), 66% (n = 517) were treated by lifestyle modification and 34% (n = 272) were treated with metformin plus lifestyle modification at enrolment. Fifty-eight per cent of participants in cohort 2 was male. Cohort 2 participants had the following characteristics at baseline: age 62 (8.1) years; BMI 30.5 (5.0) kg/m(2); fasting glucose 7.2 (1.4) mmol/l; 2 h glucose 8.6 (2.8) mmol/l. At the final follow-up examination, the participants' clinical characteristics were as follows: fasting glucose 7.9 (2.0) mmol/l; 2 h mixed-meal tolerance test glucose 9.9 (3.4) mmol/l.Conclusions/interpretation: The IMI DIRECT cohorts are intensely characterised, with a wide-variety of metabolically relevant measures assessed prospectively. We anticipate that the cohorts, made available through managed access, will provide a powerful resource for biomarker discovery, multivariate aetiological analyses and reclassification of patients for the prevention and treatment of type 2 diabetes.
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| 4. |
- Kurbasic, Azra, et al.
(författare)
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Maternal Hypertensive Disorders of Pregnancy and Offspring Risk of Hypertension : A Population-Based Cohort and Sibling Study
- 2019
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Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 32:4, s. 331-334
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women with a history of hypertensive disorders of pregnancy (HDP) are at increased risk of hypertension, cardiovascular disease, and type 2 diabetes. Offspring from pregnancies complicated by HDP also have worse cardiometabolic status in childhood and young adulthood, but the offspring risk of clinical hypertension in adulthood is largely unknown.METHODS: We studied 13,893 first-born adult offspring (49.4% female) who attended a structured population-based primary care visit (The Västerbotten Health Survey) at age 40 years in Sweden between 1994 and 2013. Data on maternal HDP were collected from a population-based birth register. We investigated the association between maternal HDP and the risk of adult offspring hypertension and worse cardiometabolic risk factor status utilizing multivariable poisson and linear regression models. We also conducted a sibling comparison, which inherently accounted for familial factors shared by siblings (N = 135).RESULTS: Offspring participants of women with HDP (N = 383, 2.8%) had increased relative risk of hypertension (1.67, 95% confidence interval: 1.38, 2.01) and also higher mean body mass index, systolic blood pressure, diastolic blood pressure, and worse 2-hour 75 g oral glucose tolerance test result at age 40 years. No difference was observed for serum cholesterol. Point estimates for the cardiometabolic risk factors were attenuated in the sibling analyses.CONCLUSION: Offspring born to mothers with a history of HDP are on an adverse cardiometabolic trajectory and should be considered as concomitant targets for primordial prevention of hypertension in the maternal post-pregnancy period.
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| 5. |
- Poveda, Alaitz, et al.
(författare)
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The heritable basis of gene–environment interactions in cardiometabolic traits
- 2017
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 60:3, s. 442-452
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Little is known about the heritable basis of gene–environment interactions in humans. We therefore screened multiple cardiometabolic traits to assess the probability that they are influenced by genotype–environment interactions. Methods: Fourteen established environmental risk exposures and 11 cardiometabolic traits were analysed in the VIKING study, a cohort of 16,430 Swedish adults from 1682 extended pedigrees with available detailed genealogical, phenotypic and demographic information, using a maximum likelihood variance decomposition method in Sequential Oligogenic Linkage Analysis Routines software. Results: All cardiometabolic traits had statistically significant heritability estimates, with narrow-sense heritabilities (h2) ranging from 24% to 47%. Genotype–environment interactions were detected for age and sex (for the majority of traits), physical activity (for triacylglycerols, 2 h glucose and diastolic BP), smoking (for weight), alcohol intake (for weight, BMI and 2 h glucose) and diet pattern (for weight, BMI, glycaemic traits and systolic BP). Genotype–age interactions for weight and systolic BP, genotype–sex interactions for BMI and triacylglycerols and genotype–alcohol intake interactions for weight remained significant after multiple test correction. Conclusions/interpretation: Age, sex and alcohol intake are likely to be major modifiers of genetic effects for a range of cardiometabolic traits. This information may prove valuable for studies that seek to identify specific loci that modify the effects of lifestyle in cardiometabolic disease.
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| 6. |
- Siddiqui, Faiza, et al.
(författare)
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Changes in dietary intake following a culturally adapted lifestyle intervention among Iraqi immigrants to Sweden at high risk of type 2 diabetes : a randomised trial
- 2017
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Ingår i: Public Health Nutrition. - 1368-9800. ; 20:15, s. 2827-2838
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the effectiveness of a culturally adapted lifestyle intervention for changing dietary intake, particularly energy, fat and fibre intakes, in the intervention group (IG) compared with the control group (CG). Design: Randomised controlled trial. Setting: IG (n 50) and CG (n 46). The IG was offered seven group sessions, including one cooking class, over a period of 4 months. The participants filled out 4 d food diaries at the start, mid and end of the study. Subjects: Iraqi-born residents of Malmö, Sweden, at increased risk for developing diabetes. Results: At baseline, participants’ fat intake was high (40 % of total energy intake (E%)). The predefined study goals of obtaining <30 E% from fat and ≥15 g fibre/4184 kJ (1000 kcal) were met by very few individuals. In the IG v. the CG, the proportion of individuals obtaining <40 E% from fat (48·4 v. 34·6 %, P=0·65), <10 E% from saturated fat (32·3 v. 11·5 %, P=0·14) and ≥10 g fibre/4184 kJ (45·2 v. 26·9 %, P=0·46) appeared to be higher at the last visit, although the differences were statistically non-significant. A trend towards decreased mean daily intakes of total energy (P=0·03), carbohydrate (P=0·06), sucrose (P=0·02) and fat (P=0·02) was observed within the IG. Differences in changes over time between the groups did not reach statistical significance. Conclusions: Although no significant differences were observed in the two groups, our data indicate that this culturally adapted programme has the potential to modify dietary intake in Middle Eastern immigrants. The high fat intake in this group should be addressed.
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| 7. |
- Siddiqui, Faiza, et al.
(författare)
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Effects of a culturally adapted lifestyle intervention on cardio-metabolic outcomes: a randomized controlled trial in Iraqi immigrants to Sweden at high risk for Type 2 diabetes
- 2017
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Ingår i: Metabolism: Clinical and Experimental. - : Elsevier BV. - 0026-0495 .- 1532-8600. ; 66, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background andAims Middle-Eastern immigrants constitute a growing proportion of the Swedish population and are at high risk for Type 2 diabetes. This calls for a more proactive preventive approach for dealing with diabetes risk in this target group. The aim was to test the effect of a culturally adapted lifestyle intervention programme on changes in lifestyle habits and cardio-metabolic outcomes comparing an intervention group with a control group receiving usual care. Methods Citizens of Malmö, Sweden born in Iraq and at high risk for Type 2 diabetes (n=636) were invited. Participation rate was 15.1%. In all, 96 participants were randomized to the intervention group (n=50) or to the control group (n=46). The intervention group was offered seven group sessions addressing healthy diet and physical activity including one cooking class. Changes in body weight, physical activity levels and cardio-metabolic outcomes were evaluated using linear mixed-effects models. Results The mean follow-up time was 3.9 and 3.5months in the intervention and control groups, respectively. The drop-out rate from baseline to the last visit was 30.0% in the intervention group (n=15) and 30.4% in the control group (n=14). The mean insulin sensitivity index increased significantly at follow-up in the intervention group compared to the control group (10.9% per month, p=0.005). The intervention group also reached a significant reduction in body weight (0.4% per month, p=0.004), body mass index (0.4% per month, p=0.004) and LDL-cholesterol (2.1% per month, p=0.036) compared to the control group. In total, 14.3% in the intervention group reached the goal to lose ≥5% of body weight versus none in the control group. Conclusions This culturally adapted lifestyle intervention programme shows a beneficial effect on insulin action, body weight reduction, as well as LDL-cholesterol reduction, in Middle-Eastern immigrants. The programme adapted to resources in primary health care provides tools for improved primary prevention and reduced cardio-metabolic risk in this high-risk group for Type 2 diabetes. © 2016 The Authors
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| 8. |
- Siddiqui, Faiza, et al.
(författare)
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Physical Activity in a Randomized Culturally Adapted Lifestyle Intervention
- 2018
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Ingår i: American Journal of Preventive Medicine. - : Elsevier BV. - 0749-3797. ; 55:2, s. 187-196
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Middle Eastern immigrants exhibit high levels of physical inactivity and are at an increased risk for Type 2 diabetes. The primary aim of this study was to examine the changes in objectively assessed physical activity levels following a culturally adapted lifestyle intervention program. The secondary aim was to examine the association between objectively assessed physical activity and insulin sensitivity. Participants: Iraqi immigrants residing in Malmo, Sweden, exhibiting one or more risk factors for Type 2 diabetes. Intervention: The intervention group (n=50) was offered a culturally adapted lifestyle intervention comprising seven group sessions including a cooking class. The control group (n=46) received usual care. Main outcome measures: Raw accelerometry data were processed by validated procedures and daily mean physical activity intensity, vector magnitude high-pass filtered (VM-HPF), was inferred. Further inferences into the number of hours/day spent in sedentary (VM-HPF <48 milli-Gs [mGs] where G=9.8 m/sec(2)) and light- (48- <163 mGs); moderate- (163- <420 mGs); and vigorous-intensity (>= 420 mGs) activities were also calculated (year of analysis was 2016-2017). Results: No difference was observed between the two groups in terms of change over time in VM-HPF. There was a significant increase in the number of hours/day spent in light intensity physical activity in the intervention group compared with the control group (beta=0.023, 95% CI=0.001, 0.045, p=0.037). The intervention group also increased the time spent in sedentary activities, with the highest VM-HPF (36- < 48 mGs) within the sedentary behavior (B=0.022, 95% CI=0.002, 0.042, p=0.03). Higher VM-HPF was significantly associated with a higher insulin sensitivity index (beta=0.014, 95% CI=0.0004, 0.025, p=0.007). Conclusions: The findings favor the culturally adapted intervention approach for addressing low physical activity levels among Middle Eastern immigrants. Replacing sedentary time with light-intensity activities could be an achievable goal and will have potential beneficial effects for diabetes prevention among this sedentary group of immigrants. Trial registration: This study was registered at www.clinicaltrials.gov NCT01420198. Am J Prev Med 2018;55(2):187-196. (C) 2018 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.
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| 9. |
- Varga, Tibor V., et al.
(författare)
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Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults
- 2017
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:4, s. 1211-1222
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants.Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD.Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.
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