Papers by Emily Sonestedt
Background:Epidemiologicstudiesofassociationsbetweenfolate intake and breast cancer are inconclus... more Background:Epidemiologicstudiesofassociationsbetweenfolate intake and breast cancer are inconclusive, but folate and other plant food nutrients appear protective in women at elevated risk. Objective: The objective was to examine the association between folate intake and the incidence of postmenopausal breast cancer. Design: This prospective study included all women aged 50 y (n 11699) from the Malmö Diet and Cancer cohort. The mean
Background:Epidemiologicstudiesofassociationsbetweenfolate intake and breast cancer are inconclus... more Background:Epidemiologicstudiesofassociationsbetweenfolate intake and breast cancer are inconclusive, but folate and other plant food nutrients appear protective in women at elevated risk. Objective: The objective was to examine the association between folate intake and the incidence of postmenopausal breast cancer. Design: This prospective study included all women aged 50 y (n 11699) from the Malmö Diet and Cancer cohort. The mean
Human molecular genetics, Jan 20, 2015
Obesity is highly heritable. Genetic variants showing robust associations with obesity traits hav... more Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. 32 BMI- and 14 waist-hip ratio (WHR)-associated SNPs were genotyped and genetic risk scores (GRS) calculated in 18 cohorts of European ancestry (n=68,317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages, fried potatoes (unfavorable). Multi-variable adjusted, linear regression within each cohort, followed by inverse variance-weighted fixed-effects meta-analysis was used to characterize: a) associations of each GRS with BMI and BMI-adjusted WHR; b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P=0.006-0.0...
Human molecular genetics, Jan 20, 2015
Obesity is highly heritable. Genetic variants showing robust associations with obesity traits hav... more Obesity is highly heritable. Genetic variants showing robust associations with obesity traits have been identified through genome-wide association studies. We investigated whether a composite score representing healthy diet modifies associations of these variants with obesity traits. 32 BMI- and 14 waist-hip ratio (WHR)-associated SNPs were genotyped and genetic risk scores (GRS) calculated in 18 cohorts of European ancestry (n=68,317). Diet score was calculated based on self-reported intakes of whole grains, fish, fruits, vegetables, nuts/seeds (favorable) and red/processed meats, sweets, sugar-sweetened beverages, fried potatoes (unfavorable). Multi-variable adjusted, linear regression within each cohort, followed by inverse variance-weighted fixed-effects meta-analysis was used to characterize: a) associations of each GRS with BMI and BMI-adjusted WHR; b) diet score modification of genetic associations with BMI and BMI-adjusted WHR. Nominally significant interactions (P=0.006-0.0...
Atherosclerosis Supplements, 2011
Objective: Obesity increases the risk of cardiovascular disease and premature death. However, not... more Objective: Obesity increases the risk of cardiovascular disease and premature death. However, not all obese subjects develop the metabolic abnormalities associated with obesity. The aim of this study was to clarify the mechanisms that induce dyslipidemia in obese subjects. Methods and Results: Stable isotope tracers were used to elucidate the pathophysiology of the dyslipidemia in hypertriglyceridemic (n = 14) and normotriglyceridemic (n = 14) obese men (with comparable body mass index and visceral fat volume) and in normotriglyceridemic non-obese men (n = 10). Liver fat was determined using proton magnetic resonance spectroscopy and subcutaneous abdominal and visceral fat were measured by magnetic resonance imaging. The results show that serum triglycerides in obese subjects are increased by the combination of increased secretion and severely impaired clearance of triglyceride-rich VLDL 1 particles. Furthermore, increased liver and subcutaneous abdominal fat are linked to increased secretion of VLDL 1 particles, whereas increased plasma levels of apolipoprotein C-III are associated with impaired clearance in obese hypertriglyceridemic subjects. Conclusion: Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects with similar levels of visceral adiposity. The results emphasize the clinical importance of measuring both abdominal obesity and traditional risk factors to properly evaluate the metabolic abnormalities in obese patients.
Atherosclerosis Supplements, 2011
Objective: Obesity increases the risk of cardiovascular disease and premature death. However, not... more Objective: Obesity increases the risk of cardiovascular disease and premature death. However, not all obese subjects develop the metabolic abnormalities associated with obesity. The aim of this study was to clarify the mechanisms that induce dyslipidemia in obese subjects. Methods and Results: Stable isotope tracers were used to elucidate the pathophysiology of the dyslipidemia in hypertriglyceridemic (n = 14) and normotriglyceridemic (n = 14) obese men (with comparable body mass index and visceral fat volume) and in normotriglyceridemic non-obese men (n = 10). Liver fat was determined using proton magnetic resonance spectroscopy and subcutaneous abdominal and visceral fat were measured by magnetic resonance imaging. The results show that serum triglycerides in obese subjects are increased by the combination of increased secretion and severely impaired clearance of triglyceride-rich VLDL 1 particles. Furthermore, increased liver and subcutaneous abdominal fat are linked to increased secretion of VLDL 1 particles, whereas increased plasma levels of apolipoprotein C-III are associated with impaired clearance in obese hypertriglyceridemic subjects. Conclusion: Dual metabolic defects are required to produce hypertriglyceridemia in obese subjects with similar levels of visceral adiposity. The results emphasize the clinical importance of measuring both abdominal obesity and traditional risk factors to properly evaluate the metabolic abnormalities in obese patients.
PloS one, 2015
It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (C... more It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (CVD) risk. Genetic susceptibility might modify the associations between dietary intakes and disease risk. The aim was to examine the association between the consumption of carbohydrate-rich foods (vegetables, fruits and berries, juice, potatoes, whole grains, refined grains, cookies and cakes, sugar and sweets, and sugar-sweetened beverages) and the risk of incident ischemic CVD (iCVD; coronary events and ischemic stroke), and whether these associations differ depending on genetic susceptibility to dyslipidemia. Among 26,445 individuals (44-74 years; 62% females) from the Malmö Diet and Cancer Study cohort, 2,921 experienced an iCVD event during a mean follow-up time of 14 years. At baseline, dietary data were collected using a modified diet history method, and clinical risk factors were measured in 4,535 subjects. We combined 80 validated genetic variants associated with triglycerides an...
PloS one, 2015
It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (C... more It is still unclear whether carbohydrate consumption is associated with cardiovascular disease (CVD) risk. Genetic susceptibility might modify the associations between dietary intakes and disease risk. The aim was to examine the association between the consumption of carbohydrate-rich foods (vegetables, fruits and berries, juice, potatoes, whole grains, refined grains, cookies and cakes, sugar and sweets, and sugar-sweetened beverages) and the risk of incident ischemic CVD (iCVD; coronary events and ischemic stroke), and whether these associations differ depending on genetic susceptibility to dyslipidemia. Among 26,445 individuals (44-74 years; 62% females) from the Malmö Diet and Cancer Study cohort, 2,921 experienced an iCVD event during a mean follow-up time of 14 years. At baseline, dietary data were collected using a modified diet history method, and clinical risk factors were measured in 4,535 subjects. We combined 80 validated genetic variants associated with triglycerides an...
The American journal of clinical nutrition, 2015
Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a cru... more Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a crucial role in the cause of type 2 diabetes (T2D). Studies indicated that replacing saturated with unsaturated fats might be favorable, and plant foods might be a better choice than animal foods. Nevertheless, epidemiologic studies suggested that dairy foods are protective. We hypothesized that, by examining dietary fat and its food sources classified according to fat type and fat content, some clarification regarding the role of dietary fat in T2D incidence could be provided. A total of 26,930 individuals (61% women), aged 45-74 y, from the Malmö Diet and Cancer cohort were included in the study. Dietary data were collected by using a modified diet-history method. During 14 y of follow-up, 2860 incident T2D cases were identified. Total intake of high-fat dairy products (regular-fat alternatives) was inversely associated with incident T2D (HR for highest compared with lowest quintiles: 0.7...
The American journal of clinical nutrition, 2015
Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a cru... more Dietary fats could affect glucose metabolism and obesity development and, thereby, may have a crucial role in the cause of type 2 diabetes (T2D). Studies indicated that replacing saturated with unsaturated fats might be favorable, and plant foods might be a better choice than animal foods. Nevertheless, epidemiologic studies suggested that dairy foods are protective. We hypothesized that, by examining dietary fat and its food sources classified according to fat type and fat content, some clarification regarding the role of dietary fat in T2D incidence could be provided. A total of 26,930 individuals (61% women), aged 45-74 y, from the Malmö Diet and Cancer cohort were included in the study. Dietary data were collected by using a modified diet-history method. During 14 y of follow-up, 2860 incident T2D cases were identified. Total intake of high-fat dairy products (regular-fat alternatives) was inversely associated with incident T2D (HR for highest compared with lowest quintiles: 0.7...
The Journal of nutrition, 2014
The unclear link between intake of polyunsaturated fatty acids (PUFAs) and risk of cardiovascular... more The unclear link between intake of polyunsaturated fatty acids (PUFAs) and risk of cardiovascular disease (CVD) could depend on genetic differences between individuals. Minor alleles of single-nucleotide polymorphisms (SNPs) in the ∆5 fatty acid desaturase (FADS) 1 gene were associated with lower blood concentrations of long-chain ω-3 (n-3) and ω-6 (n-6) PUFAs, indicating an associated loss of function effect. We examined whether the SNP rs174546 in FADS1 modifies the association between PUFA intakes and CVD risk. We included 24,032 participants (62% women, aged 44-74 y) from the Malmö Diet and Cancer cohort without prevalent CVD and diabetes. During a mean follow-up of 14 y, 2648 CVD cases were identified. Diet was assessed by a modified diet history method. A borderline interaction was observed between the α-linolenic acid (ALA) (18:3n-3)-to-linoleic acid (LA) (18:2n-6) intake ratio and FADS1 genotype on CVD incidence (P = 0.06). The ALA-to-LA intake ratio was inversely associated...
The Prostate, 2014
Variation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2... more Variation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2 diabetes (T2D), may play a role in prostate cancer (PCa) depending on lifestyle factors. The aims of this study were to determine if TCF7L2 rs7903146 is associated with risk of PCa and if the association is modified by lifestyle factors independently of T2D status. We prospectively followed 8,558 men in the Malmö Diet and Cancer Study from baseline 1991-1996 until end of 2009. Cox regression models were used to assess the association between rs7903146 T2D-risk allele (T) and PCa. Effect modification by incident T2D status, fasting glucose levels, dietary, and lifestyle risk factors were tested. During follow-up 855 incident PCa cases were registered. We observed a non-significant tendency for the TCF7L2 variant to associate with higher risk of PCa, which was unaffected by adjustment for incident T2D (HR = 1.24; 95% CI: 0.96, 1.60; P = 0.079) but more pronounced among subjects who develo...
The Prostate, 2014
Variation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2... more Variation in transcription factor 7-like 2 (TCF7L2), the strongest genetic risk factor for type 2 diabetes (T2D), may play a role in prostate cancer (PCa) depending on lifestyle factors. The aims of this study were to determine if TCF7L2 rs7903146 is associated with risk of PCa and if the association is modified by lifestyle factors independently of T2D status. We prospectively followed 8,558 men in the Malmö Diet and Cancer Study from baseline 1991-1996 until end of 2009. Cox regression models were used to assess the association between rs7903146 T2D-risk allele (T) and PCa. Effect modification by incident T2D status, fasting glucose levels, dietary, and lifestyle risk factors were tested. During follow-up 855 incident PCa cases were registered. We observed a non-significant tendency for the TCF7L2 variant to associate with higher risk of PCa, which was unaffected by adjustment for incident T2D (HR = 1.24; 95% CI: 0.96, 1.60; P = 0.079) but more pronounced among subjects who develo...
PloS one, 2012
The aim of the study was to examine associations between intake of macronutrients and dietary fib... more The aim of the study was to examine associations between intake of macronutrients and dietary fiber and incident ischemic cardiovascular disease (iCVD) in men and women. We used data from 8,139 male and 12,535 female participants (aged 44-73 y) of the Swedish population-based Malmö Diet and Cancer cohort. The participants were without history of CVD and diabetes mellitus, and had reported stable dietary habits in the study questionnaire. Diet was assessed by a validated modified diet history method, combining a 7-d registration of cooked meals and cold beverages, a 168-item food questionnaire (covering other foods and meal patterns), and a 1-hour diet interview. Sociodemographic and lifestyle data were collected by questionnaire. iCVD cases, which included coronary events (myocardial infarctions or deaths from chronic ischemic heart disease) and ischemic strokes, were ascertained via national and local registries. Nutrient-disease associations were examined by multivariate Cox regre...
European review for medical and pharmacological sciences, 2011
The etiology of common obesity is complex, because many genetic, environmental and metabolic fact... more The etiology of common obesity is complex, because many genetic, environmental and metabolic factors might act. Alterations of the normal leptin receptor gene be involved in the development of obesity. The polymorphism on codon 656 produces a change in charge, making this change a possibility to be functional. The aim of our study was to investigate the relationship between metabolic syndrome and Lys656Asn polymorphism in obese patients. A population of 714 obese patients (body mass index > 30) was analyzed in cross-sectional survey. A bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. Four hundred and seventy eight patients (66.9%) had the genotype Lys656/Lys 656 (wild group), whereas 236 (33.1%) had either the genotype Lys656/Asn656 (212 patients, 29.7%) or the genotype Asn656/Asn656 (24 patients, 3.4%) (mutant group). Prevalence of metabolic syndrome (MS) with ATP III definition was ...
European review for medical and pharmacological sciences, 2011
The etiology of common obesity is complex, because many genetic, environmental and metabolic fact... more The etiology of common obesity is complex, because many genetic, environmental and metabolic factors might act. Alterations of the normal leptin receptor gene be involved in the development of obesity. The polymorphism on codon 656 produces a change in charge, making this change a possibility to be functional. The aim of our study was to investigate the relationship between metabolic syndrome and Lys656Asn polymorphism in obese patients. A population of 714 obese patients (body mass index > 30) was analyzed in cross-sectional survey. A bioimpedance, blood pressure, a serial assessment of nutritional intake with 3 days written food records and biochemical analysis were performed. Four hundred and seventy eight patients (66.9%) had the genotype Lys656/Lys 656 (wild group), whereas 236 (33.1%) had either the genotype Lys656/Asn656 (212 patients, 29.7%) or the genotype Asn656/Asn656 (24 patients, 3.4%) (mutant group). Prevalence of metabolic syndrome (MS) with ATP III definition was ...
International journal of obesity (2005), 2011
We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity... more We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity, on fat mass, lean mass and mortality. Among 22,799 individuals (44-74 years) in the population-based Malmö diet and cancer cohort that were genotyped for rs9939609 in FTO and had information on dietary intake (from a modified diet history method) and no history of diabetes, cancer or cardiovascular disease, 2255 deaths (including 1100 cancer and 674 cardiovascular deaths) occurred during 12.0 years of follow-up. Leisure-time physical activity was determined from a list of 17 different physical activities in a questionnaire. Body composition was measured using bioelectric impedance method. FTO genotype associated strongly with both fat mass and lean mass (P(trend) <1 × 10(-16) for both) but we found only significant interactions with fat intake, or physical activity, on fat mass (P(interaction)=0.01 and 0.004). No significant interaction between FTO genotype and fat intake (P(interac...
International journal of obesity (2005), 2011
We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity... more We wanted to explore if FTO genotype interacts with fat intake, or leisure-time physical activity, on fat mass, lean mass and mortality. Among 22,799 individuals (44-74 years) in the population-based Malmö diet and cancer cohort that were genotyped for rs9939609 in FTO and had information on dietary intake (from a modified diet history method) and no history of diabetes, cancer or cardiovascular disease, 2255 deaths (including 1100 cancer and 674 cardiovascular deaths) occurred during 12.0 years of follow-up. Leisure-time physical activity was determined from a list of 17 different physical activities in a questionnaire. Body composition was measured using bioelectric impedance method. FTO genotype associated strongly with both fat mass and lean mass (P(trend) <1 × 10(-16) for both) but we found only significant interactions with fat intake, or physical activity, on fat mass (P(interaction)=0.01 and 0.004). No significant interaction between FTO genotype and fat intake (P(interac...
Genes & Nutrition, 2013
Gene-environment interactions need to be studied to better understand the obesity. We aimed at de... more Gene-environment interactions need to be studied to better understand the obesity. We aimed at determining whether genetic susceptibility to obesity associates with diet intake levels and whether diet intakes modify the genetic susceptibility. In 29,480 subjects of the population-based Malmö Diet and Cancer Study (MDCS), we first assessed association between 16 genome-wide association studies identified obesity-related single-nucleotide polymorphisms (SNPs) with body mass index (BMI) and associated traits. We then conducted association analyses between a genetic risk score (GRS) comprising of 13 replicated SNPs and the individual SNPs, and relative dietary intakes of fat, carbohydrates, protein, fiber and total energy intake, as well as interaction analyses on BMI and associated traits among 26,107 nondiabetic MDCS participants. GRS associated strongly with increased BMI (P = 3.6 9 10 -34 ), fat mass (P = 6.3 9 10 -28 ) and fat-free mass (P = 1.3 9 10 -24 ). Higher GRS associated with lower total energy intake (P = 0.001) and higher intake of fiber (P = 2.3 9 10 -4 ). No significant interactions were observed between GRS and the studied dietary intakes on BMI or related traits. Of the individual SNPs, after correcting for multiple comparisons, NEGR1 rs2815752 associated with diet intakes and BDNF rs4923461 showed interaction with protein intake on BMI. In conclusion, our study does not provide evidence for a major role for macronutrient-, fiber-or total energy intake levels in modifying genetic susceptibility to obesity measured as GRS. However, our data suggest that the number of risk alleles as well as some of the individual obesity loci may have a role in regulation of food and energy intake and that some individual loci may interact with diet. Low physical activity accentuates the effect of the FTO rs9939609 polymorphism on body fat accumulation. Diabetes 57 : 95-101. Genes Nutr 123 Bauer F, Elbers CC, Adan RA, Loos RJ, Onland-Moret NC, Grobbee DE, van Vliet-Ostaptchouk JV, Wijmenga C, van der Schouw YT (2009) Obesity genes identified in genome-wide association studies are associated with adiposity measures and potentially with nutrient-specific food preference. Am J Clin Nutr 90(4):951-959. Loos RJ (2012) Evaluation of common genetic variants identified by GWAS for early onset and morbid obesity in population-based samples. Int J Obes (Lond).
European Journal of Clinical Nutrition, 2008
Objectives:The aim of this study was to examine the variation of enterolactone from fasting and n... more Objectives:The aim of this study was to examine the variation of enterolactone from fasting and non-fasting blood of middle-aged healthy women eating a normal diet to determine the usefulness of a single sample in epidemiological studies.Subjects and methods:Twenty-six women born between 1940 and 1950 were recruited within the Malmö Diet and Cancer cohort. Three non-fasting and two overnight fasting samples
Uploads
Papers by Emily Sonestedt