| 51. |
- Ried, Janina S., et al.
(författare)
-
A principal component meta-analysis on multiple anthropometric traits identifies novel loci for body shape
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Large consortia have revealed hundreds of genetic loci associated with anthropometric traits, one trait at a time. We examined whether genetic variants affect body shape as a composite phenotype that is represented by a combination of anthropometric traits. We developed an approach that calculates averaged PCs (AvPCs) representing body shape derived from six anthropometric traits (body mass index, height, weight, waist and hip circumference, waist-to-hip ratio). The first four AvPCs explain >99% of the variability, are heritable, and associate with cardiometabolic outcomes. We performed genome-wide association analyses for each body shape composite phenotype across 65 studies and meta-analysed summary statistics. We identify six novel loci: LEMD2 and CD47 for AvPC1, RPS6KA5/C14orf159 and GANAB for AvPC3, and ARL15 and ANP32 for AvPC4. Our findings highlight the value of using multiple traits to define complex phenotypes for discovery, which are not captured by single-trait analyses, and may shed light onto new pathways.
|
|
| 52. |
- Salamone, Dominic, et al.
(författare)
-
Fatty acid composition of cholesterol esters reflects dietary fat intake after dietary interventions in a multinational population
- 2023
-
Ingår i: Journal of Clinical Lipidology. - : Elsevier. - 1933-2874 .- 1876-4789. ; 17:4, s. 466-474
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe effects of different dietary fatty acids (FA) on cardiovascular risk still needs clarification. Plasma lipids composition may be a biomarker of FA dietary intake.PurposeTo evaluate in a composite population the relationships between changes in dietary fat intake and changes in FA levels in serum cholesterol esters.MethodsIn a multinational, parallel-design, dietary intervention (KANWU study), dietary intakes (3-day food record) and FA composition of serum cholesterol esters (gas-liquid chromatography) were evaluated at baseline and after 3 months in 162 healthy individuals, randomly assigned to a diet containing a high proportion of saturated (SFA) or monounsaturated (MUFA) fat, with a second random assignment to fish oil or placebo supplements.ResultsMain differences in serum lipid composition after the two diets included saturated (especially myristic, C14:0, and pentadecanoic, C15:0) and monounsaturated (oleic acid, C18:1 n-9) FA. C14:0 and C15:0 were related to SFA intake, while C18:1 n-9 was associated with MUFA intake. Fish oil supplementation induced a marked increase in eicosapentaenoic (C20:5 n-3) and docosahexaenoic (C22:6 n-3) acids. After the 3-month intervention, Δ-9 desaturase activity, calculated as palmitoleic acid/palmitic acid (C16:1/C16:0) ratio, was more reduced after the MUFA (0.31±0.10 vs 0.25±0.09, p<0.0001) than SFA diet (0.31±0.09 vs 0.29±0.08, p=0.006), with a statistically significant difference between the two groups (p<0.0001).ConclusionsThis study shows that serum cholesterol ester FA composition can be used during randomized controlled trials as an objective indicator of adherence to experimental diets based on saturated and monounsaturated fat modifications, as well as fish oil supplementation.
|
|
| 53. |
- Schwab, Ursula, et al.
(författare)
-
Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer : a systematic review
- 2014
-
Ingår i: Food & Nutrition Research. - : SNF Swedish Nutrition Foundation. - 1654-6628 .- 1654-661X. ; 58, s. 25145-
-
Forskningsöversikt (refereegranskat)abstract
- The effects of both the amount and quality of dietary fat have been studied intensively during the past decades. Previously, low-fat diets were recommended without much attention to the quality of fat, whereas there is general emphasis on the quality of fat in current guidelines. The objective of this systematic review (SR) was to assess the evidence of an effect of the amount and type of dietary fat on body weight (BW), risk factors, and risk of non-communicable diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and cancer in healthy subjects or subjects at risk for these diseases. This work was performed in the process of updating the fourth edition of the Nordic Nutrition Recommendations from 2004. The literature search was performed in October 2010 covering articles published since January 2000. A complementary search was done in February 2012 covering literature until December 2011. Two authors independently selected articles for inclusion from a total of about 16,000 abstracts according to predefined criteria. Randomized controlled trials (RCT) and prospective cohort studies (PCS) were included as well as nested case control studies. A few retrospective case control studies were also included when limited or no data were available from other study types. Altogether 607 articles were quality graded and the observed effects in these papers were summarized. Convincing evidence was found that partial replacement of saturated fat (SFA) with polyunsaturated fat (PUFA) or monounsaturated fat (MUFA) lowers fasting serum/plasma total and LDL cholesterol concentrations. The evidence was probable for a decreasing effect of fish oil on concentration of serum/plasma total triglycerides as compared with MUFA. Beneficial effect of MUFA both on insulin sensitivity and fasting plasma/serum insulin concentration was considered as probable in comparisons of MUFA and carbohydrates versus SFA, whereas no effect was found on fasting glucose concentration in these comparisons. There was probable evidence for a moderate direct association between total fat intake and BW. Furthermore, there was convincing evidence that partial replacement of SFA with PUFA decreases the risk of CVD, especially in men. This finding was supported by an association with biomarkers of PUFA intake; the evidence of a beneficial effect of dietary total PUFA, n-6 PUFA, and linoleic acid (LA) on CVD mortality was limited suggestive. Evidence for a direct association between total fat intake and risk of T2DM was inconclusive, whereas there was limited-suggestive evidence from biomarker studies that LA is inversely associated with the risk of T2DM. However, there was limited-suggestive evidence in biomarker studies that odd-chain SFA found in milk fat and fish may be inversely related to T2DM, but these associations have not been supported by controlled studies. The evidence for an association between dietary n-3 PUFA and T2DM was inconclusive. Evidence for effects of fat on major types of cancer was inconclusive regarding both the amount and quality of dietary fat, except for prostate cancer where there was limited-suggestive evidence for an inverse association with intake of ALA and for ovarian cancer for which there was limited-suggestive evidence for a positive association with intake of SFA. This SR reviewed a large number of studies focusing on several different health outcomes. The time period covered by the search may not have allowed obtaining the full picture of the evidence in all areas covered by this SR. However, several SRs and meta-analyses that covered studies published before year 2000 were evaluated, which adds confidence to the results. Many of the investigated questions remain unresolved, mainly because of few studies on certain outcomes, conflicting results from studies, and lack of high quality-controlled studies. There is thus an evident need of highly controlled RCT and PCS with sufficient number of subjects and long enough duration, specifically regarding the effects of the amount and quality of dietary fat on insulin sensitivity, T2DM, low-grade inflammation, and blood pressure. New metabolic and other potential risk markers and utilization of new methodology in the area of lipid metabolism may provide new insight.
|
|
| 54. |
- Schwab, Ursula, et al.
(författare)
-
Triacylglycerol fatty acid composition in diet-induced weight loss in subjects with abnormal glucose metabolism : the GENOBIN study
- 2008
-
Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 3:7
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The effect of weight loss on different plasma lipid subclasses at the molecular level is unknown. The aim of this study was to examine whether a diet-induced weight reduction result in changes in the extended plasma lipid profiles (lipidome) in subjects with features of metabolic syndrome in a 33-week intervention.METHODOLOGY/PRINCIPAL FINDINGS: Plasma samples of 9 subjects in the weight reduction group and 10 subjects in the control group were analyzed using mass spectrometry based lipidomic and fatty acid analyses. Body weight decreased in the weight reduction group by 7.8+/-2.9% (p<0.01). Most of the serum triacylglycerols and phosphatidylcholines were reduced. The decrease in triacylglycerols affected predominantly the saturated short chain fatty acids. This decrease of saturated short chain fatty acid containing triacylglycerols correlated with the increase of insulin sensitivity. However, levels of several longer chain fatty acids, including arachidonic and docosahexanoic acid, were not affected by weight loss. Levels of other lipids known to be associated with obesity such as sphingolipids and lysophosphatidylcholines were not altered by weight reduction.CONCLUSIONS/SIGNIFICANCE: Diet-induced weight loss caused significant changes in global lipid profiles in subjects with abnormal glucose metabolism. The observed changes may affect insulin sensitivity and glucose metabolism in these subjects.TRIAL REGISTRATION: ClinicalTrials.gov NCT00621205.
|
|
| 55. |
- Scott, Robert A., et al.
(författare)
-
Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:9, s. 991-1005
-
Tidskriftsartikel (refereegranskat)abstract
- Through genome-wide association meta-analyses of up to 133,010 individuals of European ancestry without diabetes, including individuals newly genotyped using the Metabochip, we have increased the number of confirmed loci influencing glycemic traits to 53, of which 33 also increase type 2 diabetes risk (q < 0.05). Loci influencing fasting insulin concentration showed association with lipid levels and fat distribution, suggesting impact on insulin resistance. Gene-based analyses identified further biologically plausible loci, suggesting that additional loci beyond those reaching genome-wide significance are likely to represent real associations. This conclusion is supported by an excess of directionally consistent and nominally significant signals between discovery and follow-up studies. Functional analysis of these newly discovered loci will further improve our understanding of glycemic control.
|
|
| 56. |
|
|
| 57. |
|
|
| 58. |
- Surendran, Praveen, et al.
(författare)
-
Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension
- 2016
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:10, s. 1151-1161
-
Tidskriftsartikel (refereegranskat)abstract
- High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used -1/4155,063 samples for independent replication. We identified 30 new blood pressure- or hypertension-associated genetic regions in the general population, including 3 rare missense variants in RBM47, COL21A1 and RRAS with larger effects (>1.5 mm Hg/allele) than common variants. Multiple rare nonsense and missense variant associations were found in A2ML1, and a low-frequency nonsense variant in ENPEP was identified. Our data extend the spectrum of allelic variation underlying blood pressure traits and hypertension, provide new insights into the pathophysiology of hypertension and indicate new targets for clinical intervention.
|
|
| 59. |
- Tolppanen, Anna-Maija, et al.
(författare)
-
History of Medically Treated Diabetes and Risk of Alzheimer Disease in a Nationwide Case-Control Study
- 2013
-
Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:7, s. 2015-2019
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Type 2 diabetes in midlife or late life increases the risk of Alzheimer disease (AD), and type 1 diabetes has been associated with a higher risk of detrimental cognitive outcomes, although studies from older adults are lacking. We investigated whether individuals with AD were more likely to have a history of diabetes than matched controls from the general aged population. RESEARCH DESIGN AND METHODS-Information on reimbursed diabetes medication (including both type 1 and 2 diabetes) of all Finnish individuals with reimbursed AD medication in 2005 (n = 28,093) and their AD-free control subjects during 1972-2005 was obtained from a special reimbursement register maintained by the Social Insurance Institute of Finland. RESULTS-The prevalence of diabetes was 11.4% in the whole study population, 10.7% (n = 3,012) among control subjects, and 12.0% (n = 3,372) among AD case subjects. People with AD were more likely to have diabetes than matched control subjects (unadjusted OR 1.14 [95% CI 1.08-1.20]), even after adjusting for cardiovascular diseases (OR 1.31 [1.22-1.41]). The associations were stronger with diabetes diagnosed at midlife (adjusted OR 1.60 [1.34-1.84] and 1.25 [1.16-1.36] for midlife and late-life diabetes, respectively). CONCLUSIONS-Individuals with clinically verified AD are more likely to have a history of clinically verified and medically treated diabetes than the general aged population, although the difference is small.
|
|
| 60. |
- Tuomainen, Marjo, et al.
(författare)
-
Quantitative assessment of betainized compounds and associations with dietary and metabolic biomarkers in the randomized study of the healthy Nordic diet (SYSDIET)
- 2019
-
Ingår i: American Journal of Clinical Nutrition. - : OXFORD UNIV PRESS. - 0002-9165 .- 1938-3207. ; 110:5, s. 1108-1118
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recently, a group of betainized compounds have been suggested to play a role in health effects in relation to a whole-grain-rich diet.Objectives: The aims of this study were to develop a quantitative mass spectrometric method for selected betainized compounds in human plasma, and to investigate their association with nutrient intake and measures of metabolic health in participants of the SYSDIET study.Methods: The SYSDIET study was a controlled randomized intervention including individuals with metabolic syndrome, where the healthy Nordic diet (HND) group increased intakes of whole grains, canola oil, berries, and fish, whereas the control diet (CD) group consumed low-fiber cereal products, milk fat, and restricted amounts of fish and berries. A quantitative LC combined with triple quadrupole MS method for betainized compounds was developed and applied to fasting plasma samples from baseline (week 0) and the end of the intervention (week 18 or 24). Concentrations of betainized compounds were correlated with intakes of selected nutrients and fiber and measures of metabolic health.Results: Pipecolic acid betaine (PAB) concentrations were significantly higher in the HND group than in the CD group (P = 0.00032) at the end of the intervention and correlated directly (P < 0.0001) with intakes of dietary fiber (r = 0.376) and a biomarker related to whole-grain rye intake, namely the ratio of alkylresorcinol C17:0 to C21:0 (r = 0.442). PAB was associated inversely with fasting plasma insulin consistently at the beginning and at the end of the intervention (P < 0.001, r = -0.300; P < 0.01, r = -0.250, respectively), as well as IL-1 receptor antagonist (P < 0.01, r = -0.232 at the beginning; P < 0.01, r = -0.236 at the end) and serum LDL/HDL cholesterol (P < 0.01, r = -0.239 at the beginning; P < 0.01, r = -0.241 at the end).Conclusions: Among adults with the metabolic syndrome, PAB plasma concentrations were associated with fasting insulin, inflammation, and lipids and were significantly increased with adoption of the HND. Further studies are needed to clarify the biological functions of betainized compounds.
|
|
