| 1. |
- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 2. |
- Locke, Adam E, et al.
(författare)
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Genetic studies of body mass index yield new insights for obesity biology.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 197-401
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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| 3. |
- Marklund, Matti, et al.
(författare)
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Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality : An Individual-Level Pooled Analysis of 30 Cohort Studies
- 2019
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 139:21, s. 2422-2436
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Tidskriftsartikel (refereegranskat)abstract
- Background:Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies.Methods:We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available).Results:In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15198 incident cardiovascular events occurred among 68659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships.Conclusions:In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.
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| 4. |
- Patel, Riyaz S., et al.
(författare)
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Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events : A GENIUS-CHD Study of Individual Participant Data
- 2019
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Ingår i: Circulation. - 2574-8300. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUSCHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction < 0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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| 5. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 6. |
- Fuks, Kateryna B., et al.
(författare)
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Arterial blood pressure and long-term exposure to traffic-related air pollution : an analysis in the European Study of Cohorts for Air Pollution Effects (ESCAPE)
- 2014
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Ingår i: Journal of Environmental Health Perspectives. - : National Institute of Environmental Health Sciences (NIEHS). - 0091-6765 .- 1552-9924. ; 122:9, s. 896-905
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Forskningsöversikt (refereegranskat)abstract
- BACKGROUND: Long-term exposure to air pollution is hypothesized to elevate arterial blood pressure (BP). The existing evidence is scarce and country-specific. OBJECTIVES: We investigated the cross-sectional association of long-term traffic-related air pollution with BP and prevalent hypertension in European populations. METHODS: Fifteen population-based cohorts, participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE), were analysed. Residential exposure to particulate matter and nitrogen oxides was modelled with land use regression using a uniform protocol. Traffic exposure was assessed with traffic indicator variables. We analysed systolic and diastolic BP in participants medicated and non-medicated with BP lowering medication (BPLM) separately, adjusting for personal and area-level risk factors and environmental noise. Prevalent hypertension was defined as ≥ 140 mmHg systolic, or ≥ 90 mmHg diastolic BP, or intake of BPLM. We combined cohort-specific results using random-effects meta-analysis. RESULTS: In the main meta-analysis of 113,926 participants, traffic load on major roads within 100 m of the residence was associated with increased systolic and diastolic BP in non-medicated participants (0.35 mmHg [95% CI: 0.02-0.68] and 0.22 mmHg [95% CI: 0.04-0.40] per 4,000,000 vehicles × m/day, respectively). The estimated odds ratio for prevalent hypertension was 1.05 [95% CI: 0.99-1.11] per 4,000,000 vehicles × m/day. Modelled air pollutants and BP were not clearly associated. CONCLUSIONS: In this first comprehensive meta-analysis of European population-based cohorts we observed a weak positive association of high residential traffic exposure with BP in non-medicated participants, and an elevated OR for prevalent hypertension. The relationship of modelled air pollutants with BP was inconsistent.
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| 7. |
- Wang, Meng, et al.
(författare)
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Long-term exposure to elemental constituents of particulate matter and cardiovascular mortality in 19 European cohorts : Results from the ESCAPE and TRANSPHORM projects
- 2014
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Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 66, s. 97-106
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Tidskriftsartikel (refereegranskat)abstract
- Background: Associations between long-term exposure to ambient particulate matter (PM) and cardiovascular (CVD) mortality have been widely recognized. However, health effects of long-term exposure to constituents of PM on total CVD mortality have been explored in a single study only. Aims: The aim of this study was to examine the association of PM composition with cardiovascular mortality. Methods: We used data from 19 European ongoing cohorts within the framework of the ESCAPE (European Study of Cohorts for Air Pollution Effects) and TRANSPHORM (Transport related Air Pollution and Health impacts Integrated Methodologies for Assessing Particulate Matter) projects. Residential annual average exposure to elemental constituents within particle matter smaller than 2.5 and 10 pm (PM2.5 and PM10) was estimated using Land Use Regression models. Eight elements representing major sources were selected a priori (copper, iron, potassium, nickel, sulfur, silicon, vanadium and zinc). Cohort-specific analyses were conducted using Cox proportional hazards models with a standardized protocol. Random-effects metaanalysis was used to calculate combined effect estimates. Results: The total population consisted of 322,291 participants, with 9545 CVD deaths. We found no statistically significant associations between any of the elemental constituents in PM2.5 or PM10 and CVD mortality in the pooled analysis. Most of the hazard ratios (HRs) were close to unity, e.g. for PM10 Fe the combined HR was 0.96 (0.84-1.09). Elevated combined HRs were found for PM2.5 Si (1.17, 95% Cl: 0.93-1.47), and S in PM2.5 (1.08,95% Cl: 0.95-1.22) and PM10 (1.09,95% Cl: 0.90-132). Conclusion: In a joint analysis of 19 European cohorts, we found no statistically significant association between long-term exposure to 8 elemental constituents of particles and total cardiovascular mortality.
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| 8. |
- Alsharari, Zayed, et al.
(författare)
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Association between carbohydrate intake and fatty acids in the de novo lipogenic pathway in serum phospholipids and adipose tissue in a population of Swedish men
- 2020
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Ingår i: European Journal of Nutrition. - : Springer Science and Business Media LLC. - 1436-6207 .- 1436-6215. ; 59:5, s. 2089-2097
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Tidskriftsartikel (refereegranskat)abstract
- Purpose Fatty acid composition in blood and adipose tissue (AT) is a useful biomarker of dietary fat quality. However, circulating saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) have been proposed to also reflect carbohydrate-induced de novo lipogenesis (DNL) and stearoyl-CoA desaturase (SCD) activity. We aimed to test the hypothesis that high carbohydrate intake is related to SFA and MUFA in serum or AT in a Swedish population. Methods Fatty acid composition was measured in serum phospholipids (PL) and AT by gas chromatography in 63-year-old men (n = 299). Carbohydrate and alcohol intake was assessed (validated 7-day food records) in relation to total SFA, 16:0 (palmitate), 16:1 (palmitoleate), and estimated SCD activity (16:1n-7/16:0-ratio) in serum PL and in AT, respectively. Results Total carbohydrate intake was inversely associated with 16:0 in PL (P = 0.005), independently of BMI. Disaccharides were non-linearly (restricted cubic splines) and weakly associated with 16:1 and SCD activity in PL (nonlinear trend,P <= 0.02) but not AT. Carbohydrate intake and SCD expression were not associated (P >= 0.08,n = 81). Alcohol intake was, however, linearly associated with 16:0 in PL (P < 0.001), and with 16:1 (P < 0.001) and SCD activity (P <= 0.005) in both PL and AT. Conclusions Higher carbohydrate intake from sugar-rich foods or beverages was not clearly reflected by higher SFA or SCD activity in serum PL or AT. Alcohol was, however, associated with higher SFA and MUFA.
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| 9. |
- Alsharari, Zayed, et al.
(författare)
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Association between carbohydrate intake and fatty acids in the de novo lipogenic pathwayin serum phospholipids and adipose tissue among 63-year old men
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- AbstractBackground: Fatty acid composition in blood and adipose tissue is useful to reflect dietary fatquality, although the utility of even-chain saturated fatty acids (SFA) and monounsaturated fatty acids (MUFA) has been debated. Since SFA also can be produced via de novo lipogenesis (DNL), and desaturated to MUFA, it has been proposed that these fatty acids may reflect carbohydrate-induced DNL. We aimed to test the hypothesis that high carbohydrate intake, especially sugars, is related to SFA and MUFA in serum and adipose tissue.Methods: Validated 7-day food records were collected and fatty acid composition in serum phospholipids (PL) and adipose tissue (AT) were measured in 63-year-old men (n=299). Stearoyl-CoA desaturate (SCD) activities in AT and PL were estimated by the palmitoleic acid (16:1) to palmitic acid (16:0) ratio. Associations of dietary carbohydrate, disaccharides, monosaccharides, carbohydrate-to-fiber ratio, and alcohol with the sum of even-chain SFA, 16:0, 16:1, and SCD activity were assessed using linear regression models with and without adjustment for BMI. Non-linear trends were evaluated using restricted cubic splines. In a subsample (n=81) with RNA measured in AT biopsies, associations of dietary carbohydrate and alcohol with SCD gene expression were assessed using linear regression models.Results: In BMI-adjusted models, intake of carbohydrates was inversely associated with palmitic acid in PL (P=0.005). Disaccharide intake was non-linearly associated with 16:1 and SCD activity in PL (P for nonlinear trend ≤0.02), with the lowest values observed in the mid tertile. Alcohol intake was linearly associated with 16:0 in PL (P<0.001) and with 16:1 (P<0.001) and SCD activity (P ≤0.005) in AT. Alcohol intake was non-linear associated (P≤0.02) with 16:1 and SCD activity in PL; with initially stable levels at lower intakes that rapidly increased at intakes above median. In the subsample, we found no associations between carbohydrate intake and SCD gene expression (P ≥0.08).Conclusion: In this Swedish population, we found no evidence to suggest that higher carbohydrate intake or sugar-rich foods or beverages is reflected by higher SFA in PL and AT.Instead, alcohol was consistently associated with higher SFA and MUFA.
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| 10. |
- Alsharari, Zayed, et al.
(författare)
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CarbohydrateIntake and Abdominal Obesity in Swedish Men
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- ABSTRACTBackground/Objectives: Associations between carbohydrates, particularly simple sugar and starch, and abdominal anthropometric measures appears controversial. However, the role of dietary carbohydrate intake in obesity and abdominal obesity has been debated, and few studies have been conducted in Nordic populations. We aim to examine the associations between carbohydrate quantity and quality, and anthropometric measures in Swedish men.Subjects/Methods: A cross-sectional investigation of 301 63-year-old men was conducted. Six men were excluded due to missing data on dietary intake and anthropometric measures, leaving 295 men for the present study. Healthy men were recruited from the Swedish 60YO cohort of men and women who had a health screening between 1997 to 1999. Carbohydrate and alcohol intake were assessed by a 7-days food record. The examination included anthropometric measurements (e. g., weight, BMI, WC, WHR, and SAD), fasting blood samples, and a comprehensive questionnaire. Spearman rank correlation and linear regression models were performed to assess relations between dietary intakes and anthropometric measures. Intakes of macronutrients were energy-adjusted according to the residual method. Logistic regression models were used to calculate odds ratios (OR) and 95% CI for abdominal obesity per intake tertiles.Results: Intakes of carbohydrate, monosaccharide, fibers, and fruits and vegetables correlated negatively with anthropometric measures of overall obesity (BMI) and AO (WC, WHR, and SAD). Total carbohydrate intake was significantly inversely associated with WHR and SAD. Likewise, monosaccharide intake was significantly associated with lower BMI, WC, WHR, and SAD. In contrast, alcohol intake was significantly associated with weight, BMI, WC, and SAD (Table 4). Alcohol intake was associated with AO (P for linear trend 0.002). Men in the highest tertile of alcohol intake were almost three times as likely to have AO compared to the men in the lowest tertile of intake, OR (95% CI): 2.93 (1.40-6.16). There was no evidence of non-linear association between the macronutrients and AO.Conclusion: In this Swedish population of older men, higher intakes of total carbohydrates and monosaccharides were associated a more favorable body fat distribution and lower abdominal adiposity. Men with higher alcohol intake were more likely to have AO as compared with a lower intake.
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