Numerous studies have investigated the prevalence and risk factors of hand eczema in the general ... more Numerous studies have investigated the prevalence and risk factors of hand eczema in the general population. These studies are of high value as they tend to be less biased than studies using clinical populations and as they are important for healthcare decision makers when they allocate resources. This study aimed to review the epidemiology of hand eczema in the general population.
BACKGROUND/OBJECTIVES: The aim was to examine the causal effect of vitamin D on serum adiponectin... more BACKGROUND/OBJECTIVES: The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach. SUBJECTS/METHODS: Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two Danish population-based studies: the Inter99 study (6405 adults, 30-60 years) conducted in 1999-2001, and the MONICA10 study (2656 adults, 41-71 years) conducted in 1993-1994. RESULTS: In the Inter99 study, serum 25(OH)D was positively associated with total adiponectin (the effect estimate in % per doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, Po0.001). Using variations in the vitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P ¼ 0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10 cohort, no significant association was observed between the serum concentrations of 25(OH)D and HMW adiponectin (the effect estimate in % per doubling of 25(OH)D was À 1.51, 95% CI: À 5.80, 2.98, P ¼ 0.50), although the instrumental variables analysis to some extent supported a positive causal association (the effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI: À 3.67, 95.20, P ¼ 0.080).
We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have a... more We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers. All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database. We screened a Danish population-based sample with available whole-exome sequencing data (n = 870) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non-carriers. Syncope data analysis between variant and non-variant carriers showed that 4 of 227 (1.8%) a...
A trans-ethnic meta-analysis of type 2 diabetes genome-wide association studies has identified se... more A trans-ethnic meta-analysis of type 2 diabetes genome-wide association studies has identified seven novel susceptibility variants in or near TMEM154, SSR1/RREB1, FAF1, POU5F1/TCF19, LPP, ARL15 and ABCB9/MPHOSPH9. The aim of our study was to investigate associations between these novel risk variants and type 2 diabetes and pre-diabetic traits in a Danish population-based study with measurements of plasma glucose and serum insulin after an oral glucose tolerance test in order to elaborate on the physiological impact of the variants. Case-control analyses were performed in up to 5,777 patients with type 2 diabetes and 7,956 individuals with normal fasting glucose levels. Quantitative trait analyses were performed in up to 5,744 Inter99 participants naïve to glucose-lowering medication. Significant associations between TMEM154-rs6813195 and the beta cell measures insulinogenic index and disposition index and between FAF1-rs17106184 and 2-hour serum insulin levels were selected for furt...
Background: Contact allergy is a major public health problem in industrialized countries. Hithert... more Background: Contact allergy is a major public health problem in industrialized countries. Hitherto, known risk factors for contact allergy have mainly included increased exposure to allergens. There are no published data on the relation between smoking and contact allergy. Objective: To investigate the association between smoking and contact allergy. Methods: The study population comprised a cross-sectional, general population-based sample of 15-to 69-year-old persons living in Copenhagen, Denmark. A total of 1056 persons (73.6% of the invited) were given a patch test (TRUE test). Contact allergy was defined as a positive patch test result to at least 1 of 23 allergens. Nickel contact allergy was defined as a positive patch test reaction to nickel. Allergic nickel contact dermatitis was defined as a history of eczema on exposure to metallic objects and a positive patch test reaction to nickel. A detailed smoking history was obtained in a questionnaire. Results: Contact allergy (adjusted odds ratio, 1.8; 95% CI, 1.2 to 2.9), nickel contact allergy (adjusted odds ratio, 2.7; 95% CI, 1.4 to 5.2), and allergic nickel contact dermatitis (adjusted odds ratio, 3.0; 95% CI, 1.5 to 6.2) were significantly associated with a smoking history of more than 15 pack-years. Moreover, these associations showed a significant dose-response relation, and they were independent of sex, age, and exposure to nickel, as reflected by a history of ear piercing. Conclusions: These data raise the hypothesis that smoking increases the risk of contact allergy. Further epidemiologic studies and investigations into the possible mechanisms are warranted. (J Allergy Clin Immunol 2003;111:980-4.)
At present, there is no European report on clinically relevant systemic reactions due to the regu... more At present, there is no European report on clinically relevant systemic reactions due to the regular use of allergen immunotherapy (AIT), administered either subcutaneously or sublingually (SCIT and SLIT, respectively) outside clinical trials. Using an electronic survey and a "harmonised terminology" according to MedDRA, we aimed to prospectively collect systemic adverse reactions due to AIT from real life clinical settings. Under the framework of the EAACI, a team of European specialists in AIT, pharmacovigilance, epidemiology and drugs regulation set up a web-based prospective pilot survey to be conducted in three European countries (France, Germany and Spain). A designated "national coordinator" was responsible for following ethics requirements relative to each country and to select at least 30 doctors per country. Patients were recruited the same day they received their first dose of either SCIT or SLIT. Patient inclusion criteria were: adults and children, with IgE mediated pollen, house dust mite, Alternaria, and/or animal dander respiratory allergies who will initiate AIT. A list of 31 symptoms terms were extracted from the MedDRA (Medical Dictionary for Regulatory Activities) dictionary to harmonize the reporting of all adverse systemic reactions in this survey. The SurveyMonkey® online instrument was used by participant doctors to submit information directly to a blinded central database. Three questionnaires were generated: i) the Doctor Questionnaire, ii) the Patient Questionnaire and iii) the Adverse Reaction Questionnaire. A handbook and a mistake report form were given to each doctor. In this paper, we describe the methodology followed.
To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to inv... more To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Mendelian randomisation meta-analysis of 56 epidemiological studies. 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5....
Background: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10... more Background: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer of allergens across the epidermis. We hypothesized that these individuals may have increased trans dermal uptake of endocrine disruptors, including phthalates. oBjectives: We investigated urinary excretion of phthalate metabolites and testicular function in young men with and without FLG loss-of-function variants in a cross-sectional study of 861 young men from the general Danish population. Methods: All men were genotyped for FLG R501X, 2282del4, and R2447X loss-of-function variants. We measured urinary concentrations of 14 phthalate metabolites and serum levels of reproductive hormones. We also evaluated semen quality. results: Sixty-five men (7.5%) carried at least one FLG-null allele. FLG-null carriers had significantly higher urinary concentrations of several phthalate metabolites, including a 33% higher concentration of MnBP (mono-n-butyl phthalate; 95% CI: 16, 51%). FLG-null variants were not significantly associated with reproductive hormones or semen quality parameters. conclusion: This study provides evidence that carriers of FLG loss-of-function alleles may have higher internal exposure to phthalates, possibly due to increased trans epidermal absorption. FLG loss-of-function variants may indicate susceptible populations for which special attention to transepidermal absorption of chemicals and medication may be warranted. citation: Joensen UN, Jørgensen N, Meldgaard M, Frederiksen H, Andersson AM, Menné T, Johansen JD, Carlsen BC, Stender S, Szecsi PB, Skakkebaek NE, Rajpert-De Meyts E, Thyssen JP. 2014. Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish men. Environ Health Perspect 122:345-350; http://dx.doi.
Background: Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortali... more Background: Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality.
Objectives: Vitamin D deficiency is common among persons with chronic obstructive pulmonary disea... more Objectives: Vitamin D deficiency is common among persons with chronic obstructive pulmonary disease (COPD). Whether vitamin D affects the development and deterioration of COPD or is a consequence of the disease lacks clarity. We investigated the association between vitamin D status and prevalent and incident COPD in the general population.
Through whole-genome sequencing of 2,630 Icelanders and imputation into ,4 Icelandic cases and 26... more Through whole-genome sequencing of 2,630 Icelanders and imputation into ,4 Icelandic cases and 267,40 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (.47%) variant in intron of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.53, P = 5.0 × 0 −2 ) and is correlated with increased CCND2 expression. Notably, this variant is also associated with both greater height and higher body mass index (.7 cm per allele, P = 5.5 × 0 −2 and 0.56 kg/m 2 per allele, P = 6.5 × 0 −7 , respectively). In addition, two missense variants in PAM, encoding p.Asp563Gly (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately higher risk of T2D (OR = .23, P = 3.9 × 0 −0 and OR = .47, P = .7 × 0 −5 , respectively), and a rare (0.20%) frameshift variant in PDX1, encoding p.Gly28Alafs*2, associates with high risk of T2D (OR = 2.27, P = 7.3 × 0 −7 ).
Background: Genetic predisposition to adiposity may interact with dietary protein in relation to ... more Background: Genetic predisposition to adiposity may interact with dietary protein in relation to changes of anthropometry.
Chemical intolerance (CI) is characterised by negative health effects attributed to a heightened ... more Chemical intolerance (CI) is characterised by negative health effects attributed to a heightened responsiveness to common airborne chemicals. This longitudinal study explored the hypothesised role of negative affect in the development and persistence of CI in a general population. A general population sample aged 19 to 72years was examined in 2006-2008 and again in 2011-2012. Longitudinal data on CI were analysed with the purpose of examining baseline negative affect as a risk factor for having developed CI at 5-year follow-up and for reporting persistent CI. Participants were classified as reporting no signs of CI, having symptoms of CI and as being a likely CI case based on self-reported reactions to 11 common chemical exposures, symptoms related to chemical exposures and daily life adjustments attributed to reactions when exposed to chemicals. A total of 69.4% of the participants who had reported CI at baseline also reported CI at follow-up. In participants with no baseline CI, 1...
Circulation. Cardiovascular genetics, Jan 24, 2015
-There are several well-established lifestyle factors influencing dyslipidemia and currently, 157... more -There are several well-established lifestyle factors influencing dyslipidemia and currently, 157 genetic susceptibility loci have been reported to be associated with serum lipid levels at genome-wide statistical significance. However, the interplay between lifestyle risk factors and these susceptibility loci has not been fully elucidated. We tested if genetic risk scores (GRS) of lipid-associated SNPs associate with fasting serum lipid traits and if the effects are modulated by lifestyle factors or estimates of metabolic health. -The SNPs were genotyped in two Danish cohorts: Inter99 (n=5,961) for discovery analyses and Health2006 (n=2,565) for replication. Based on published effect sizes of SNPs associated with circulating fasting levels of total cholesterol, LDL-cholesterol, HDL-cholesterol or triglyceride, four weighted GRS (wGRS) were constructed. In a cross-sectional design, we investigated if the effect of these wGRSs on lipid levels were modulated by diet, alcohol consumption, physical activity and smoking or the individual metabolic health status as estimated from BMI, waist circumference and insulin resistance assessed using HOMA-IR. All four lipid wGRSs associated strongly with their respective trait (from P=3.3×10(-69) to P=1.1×10(-123)). We found interactions between the triglyceride wGRS and BMI and waist circumference on fasting triglyceride levels in Inter99 and replicated these findings in Health2006 (Pinteraction=9.8×10(-5) and 2.0×10(-5), respectively in combined analysis). -Our findings suggest that individuals who are obese may be more susceptible to the cumulative genetic burden of triglyceride SNPs. Therefore, it is suggested that especially these genetically at-risk individuals may benefit more from targeted interventions aiming at obesity prevention.
European journal of preventive cardiology, Jan 3, 2014
Excessive salt intake causes increased blood pressure which is considered the leading risk for pr... more Excessive salt intake causes increased blood pressure which is considered the leading risk for premature death. One major challenge when evaluating associations between daily salt intake and markers of non-communicable diseases is that a high daily salt intake correlates with obesity, which is also a well described risk factor for poor cardiometabolic outcome. The aim of this study was to evaluate the relationship of estimated daily salt intake with blood pressure and blood lipids and to investigate the effect of taking different measures of obesity into account. We included 3294 men and women aged 18-69 years from a general population based study in Copenhagen, Denmark. Estimated 24-hour sodium excretion was calculated by measurements of creatinine and sodium concentration in spot urine in combination with information of sex, age, height and weight. The relations of estimated 24-hour sodium excretion with blood pressure and blood lipids were evaluated by linear regression models. T...
The aim of this paper was to identify the extent of socioeconomic inequality in participation at ... more The aim of this paper was to identify the extent of socioeconomic inequality in participation at baseline and follow-up visits. The Inter99 study is a randomized intervention with the aim of investigating the effects of an individualized lifestyle consultation on ischaemic heart disease (IHD). The study comprised 61,301 persons of which 13,016 were assigned to the intervention group. The rest formed the control group. All those in the intervention group were invited to participate in health examinations, risk assessments, and lifestyle consultations. Participants at high risk of IHD were invited to follow-up visits after 1, 3, and 5 years. Data on five socioeconomic factors were retrieved from nationwide registers. For each socioeconomic factor we estimated the relative risks and relative index of inequality of participation at the baseline visit and among high-risk participants at follow-up visits. In addition, we conducted analyses of trends in socioeconomic inequality in participation across follow-up visits. Participation rates were 53% at baseline and 61-65% at the three follow-up visits. There was strong socioeconomic inequality in participation at baseline, with increasing probability of participation found with increasing level of socioeconomic position. This was smaller at follow-up visits. Except for education and housing tenure, there was an increase in socioeconomic inequality in participation across follow-up visits. We found strong socioeconomic inequality in participation at baseline and follow-up visits. Effort should be made to increase participation in individualized lifestyle interventions among persons of low socioeconomic position. Otherwise, the consequence may be increased socioeconomic inequality in IHD.
Common diseases like essential hypertension or diabetes mellitus are complex as they are polygeni... more Common diseases like essential hypertension or diabetes mellitus are complex as they are polygenic in nature, such that each genetic variation only has a small influence on the disease. Genes operates in integrated networks providing the blue-print for all biological processes and conditional of the complex genotype determines the state and dynamics of any trait, which may be modified to various extent by non-genetic factors. Thus, diseases are heterogenous ensembles of conditions with a common endpoint. Numerous studies have been performed to define genes of importance for a trait or disease, but only a few genes with small effect have been identified. The major reasons for this modest progress is the unresolved heterogeneity of the regulation of blood pressure and the shortcomings of the prevailing monogenic approach to capture genetic effects in a polygenic condition. Here, a two-step procedure is presented in which physiological heterogeneity is disentangled and genetic effects ...
Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impac... more Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on allcause mortality in people aged Z60 years.
Alcoholism: Clinical and Experimental Research, 2008
Background: A number of studies have shown that self-reported alcohol intake is positively associ... more Background: A number of studies have shown that self-reported alcohol intake is positively associated with total serum immunoglobin E (IgE) levels. The purpose of the present study was to investigate the association of self-reported alcohol consumption and different biomarkers of alcohol exposure to total serum IgE levels in a general adult population.
Numerous studies have investigated the prevalence and risk factors of hand eczema in the general ... more Numerous studies have investigated the prevalence and risk factors of hand eczema in the general population. These studies are of high value as they tend to be less biased than studies using clinical populations and as they are important for healthcare decision makers when they allocate resources. This study aimed to review the epidemiology of hand eczema in the general population.
BACKGROUND/OBJECTIVES: The aim was to examine the causal effect of vitamin D on serum adiponectin... more BACKGROUND/OBJECTIVES: The aim was to examine the causal effect of vitamin D on serum adiponectin using a multiple instrument Mendelian randomization approach. SUBJECTS/METHODS: Serum 25-hydroxy vitamin D (25(OH)D) and serum total or high molecular weight (HMW) adiponectin were measured in two Danish population-based studies: the Inter99 study (6405 adults, 30-60 years) conducted in 1999-2001, and the MONICA10 study (2656 adults, 41-71 years) conducted in 1993-1994. RESULTS: In the Inter99 study, serum 25(OH)D was positively associated with total adiponectin (the effect estimate in % per doubling of 25(OH)D was 4.78, 95% CI: 1.96, 7.68, Po0.001). Using variations in the vitamin D-binding protein gene and the filaggrin gene as instrumental variables, the causal effect in % was estimated to 61.46, 95% CI: 17.51, 120.28, P ¼ 0.003 higher adiponectin per doubling of 25(OH)D. In the MONICA10 cohort, no significant association was observed between the serum concentrations of 25(OH)D and HMW adiponectin (the effect estimate in % per doubling of 25(OH)D was À 1.51, 95% CI: À 5.80, 2.98, P ¼ 0.50), although the instrumental variables analysis to some extent supported a positive causal association (the effect estimate in % per doubling of 25(OH)D was 37.13, 95% CI: À 3.67, 95.20, P ¼ 0.080).
We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have a... more We studied whether variants previously associated with congenital long QT syndrome (cLQTS) have an effect on the QTc interval in a Danish population sample. Furthermore, we assessed whether carriers of variants in cLQTS-associated genes are more prone to experience syncope compared with non-carriers and whether carriers have an increased mortality compared with non-carriers. All genetic variants previously associated with cLQTS were surveyed using the Human Gene Mutation Database. We screened a Danish population-based sample with available whole-exome sequencing data (n = 870) and genotype array data (n = 6161) for putative cLQTS genetic variants. In total, 33 of 1358 variants previously reported to associate with cLQTS were identified. Of these, 10 variants were found in 8 or more individuals. Electrocardiogram results showed normal mean QTc intervals in carriers compared with non-carriers. Syncope data analysis between variant and non-variant carriers showed that 4 of 227 (1.8%) a...
A trans-ethnic meta-analysis of type 2 diabetes genome-wide association studies has identified se... more A trans-ethnic meta-analysis of type 2 diabetes genome-wide association studies has identified seven novel susceptibility variants in or near TMEM154, SSR1/RREB1, FAF1, POU5F1/TCF19, LPP, ARL15 and ABCB9/MPHOSPH9. The aim of our study was to investigate associations between these novel risk variants and type 2 diabetes and pre-diabetic traits in a Danish population-based study with measurements of plasma glucose and serum insulin after an oral glucose tolerance test in order to elaborate on the physiological impact of the variants. Case-control analyses were performed in up to 5,777 patients with type 2 diabetes and 7,956 individuals with normal fasting glucose levels. Quantitative trait analyses were performed in up to 5,744 Inter99 participants naïve to glucose-lowering medication. Significant associations between TMEM154-rs6813195 and the beta cell measures insulinogenic index and disposition index and between FAF1-rs17106184 and 2-hour serum insulin levels were selected for furt...
Background: Contact allergy is a major public health problem in industrialized countries. Hithert... more Background: Contact allergy is a major public health problem in industrialized countries. Hitherto, known risk factors for contact allergy have mainly included increased exposure to allergens. There are no published data on the relation between smoking and contact allergy. Objective: To investigate the association between smoking and contact allergy. Methods: The study population comprised a cross-sectional, general population-based sample of 15-to 69-year-old persons living in Copenhagen, Denmark. A total of 1056 persons (73.6% of the invited) were given a patch test (TRUE test). Contact allergy was defined as a positive patch test result to at least 1 of 23 allergens. Nickel contact allergy was defined as a positive patch test reaction to nickel. Allergic nickel contact dermatitis was defined as a history of eczema on exposure to metallic objects and a positive patch test reaction to nickel. A detailed smoking history was obtained in a questionnaire. Results: Contact allergy (adjusted odds ratio, 1.8; 95% CI, 1.2 to 2.9), nickel contact allergy (adjusted odds ratio, 2.7; 95% CI, 1.4 to 5.2), and allergic nickel contact dermatitis (adjusted odds ratio, 3.0; 95% CI, 1.5 to 6.2) were significantly associated with a smoking history of more than 15 pack-years. Moreover, these associations showed a significant dose-response relation, and they were independent of sex, age, and exposure to nickel, as reflected by a history of ear piercing. Conclusions: These data raise the hypothesis that smoking increases the risk of contact allergy. Further epidemiologic studies and investigations into the possible mechanisms are warranted. (J Allergy Clin Immunol 2003;111:980-4.)
At present, there is no European report on clinically relevant systemic reactions due to the regu... more At present, there is no European report on clinically relevant systemic reactions due to the regular use of allergen immunotherapy (AIT), administered either subcutaneously or sublingually (SCIT and SLIT, respectively) outside clinical trials. Using an electronic survey and a "harmonised terminology" according to MedDRA, we aimed to prospectively collect systemic adverse reactions due to AIT from real life clinical settings. Under the framework of the EAACI, a team of European specialists in AIT, pharmacovigilance, epidemiology and drugs regulation set up a web-based prospective pilot survey to be conducted in three European countries (France, Germany and Spain). A designated "national coordinator" was responsible for following ethics requirements relative to each country and to select at least 30 doctors per country. Patients were recruited the same day they received their first dose of either SCIT or SLIT. Patient inclusion criteria were: adults and children, with IgE mediated pollen, house dust mite, Alternaria, and/or animal dander respiratory allergies who will initiate AIT. A list of 31 symptoms terms were extracted from the MedDRA (Medical Dictionary for Regulatory Activities) dictionary to harmonize the reporting of all adverse systemic reactions in this survey. The SurveyMonkey® online instrument was used by participant doctors to submit information directly to a blinded central database. Three questionnaires were generated: i) the Doctor Questionnaire, ii) the Patient Questionnaire and iii) the Adverse Reaction Questionnaire. A handbook and a mistake report form were given to each doctor. In this paper, we describe the methodology followed.
To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to inv... more To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. Mendelian randomisation meta-analysis of 56 epidemiological studies. 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5....
Background: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10... more Background: Filaggrin is an epidermal protein that is crucial for skin barrier function. Up to 10% of Europeans and 5% of Asians carry at least one null allele in the filaggrin gene (FLG). Reduced expression of filaggrin in carriers of the null allele is associated with facilitated transfer of allergens across the epidermis. We hypothesized that these individuals may have increased trans dermal uptake of endocrine disruptors, including phthalates. oBjectives: We investigated urinary excretion of phthalate metabolites and testicular function in young men with and without FLG loss-of-function variants in a cross-sectional study of 861 young men from the general Danish population. Methods: All men were genotyped for FLG R501X, 2282del4, and R2447X loss-of-function variants. We measured urinary concentrations of 14 phthalate metabolites and serum levels of reproductive hormones. We also evaluated semen quality. results: Sixty-five men (7.5%) carried at least one FLG-null allele. FLG-null carriers had significantly higher urinary concentrations of several phthalate metabolites, including a 33% higher concentration of MnBP (mono-n-butyl phthalate; 95% CI: 16, 51%). FLG-null variants were not significantly associated with reproductive hormones or semen quality parameters. conclusion: This study provides evidence that carriers of FLG loss-of-function alleles may have higher internal exposure to phthalates, possibly due to increased trans epidermal absorption. FLG loss-of-function variants may indicate susceptible populations for which special attention to transepidermal absorption of chemicals and medication may be warranted. citation: Joensen UN, Jørgensen N, Meldgaard M, Frederiksen H, Andersson AM, Menné T, Johansen JD, Carlsen BC, Stender S, Szecsi PB, Skakkebaek NE, Rajpert-De Meyts E, Thyssen JP. 2014. Associations of filaggrin gene loss-of-function variants with urinary phthalate metabolites and testicular function in young Danish men. Environ Health Perspect 122:345-350; http://dx.doi.
Background: Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortali... more Background: Urine albumin creatinine ratio, UACR, is positively associated with all-cause mortality, cardiovascular disease and diabetes in observational studies. Whether a high UACR is also associated with other causes of death is unclear. We investigated the association between UACR and cause-specific mortality.
Objectives: Vitamin D deficiency is common among persons with chronic obstructive pulmonary disea... more Objectives: Vitamin D deficiency is common among persons with chronic obstructive pulmonary disease (COPD). Whether vitamin D affects the development and deterioration of COPD or is a consequence of the disease lacks clarity. We investigated the association between vitamin D status and prevalent and incident COPD in the general population.
Through whole-genome sequencing of 2,630 Icelanders and imputation into ,4 Icelandic cases and 26... more Through whole-genome sequencing of 2,630 Icelanders and imputation into ,4 Icelandic cases and 267,40 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (.47%) variant in intron of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.53, P = 5.0 × 0 −2 ) and is correlated with increased CCND2 expression. Notably, this variant is also associated with both greater height and higher body mass index (.7 cm per allele, P = 5.5 × 0 −2 and 0.56 kg/m 2 per allele, P = 6.5 × 0 −7 , respectively). In addition, two missense variants in PAM, encoding p.Asp563Gly (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately higher risk of T2D (OR = .23, P = 3.9 × 0 −0 and OR = .47, P = .7 × 0 −5 , respectively), and a rare (0.20%) frameshift variant in PDX1, encoding p.Gly28Alafs*2, associates with high risk of T2D (OR = 2.27, P = 7.3 × 0 −7 ).
Background: Genetic predisposition to adiposity may interact with dietary protein in relation to ... more Background: Genetic predisposition to adiposity may interact with dietary protein in relation to changes of anthropometry.
Chemical intolerance (CI) is characterised by negative health effects attributed to a heightened ... more Chemical intolerance (CI) is characterised by negative health effects attributed to a heightened responsiveness to common airborne chemicals. This longitudinal study explored the hypothesised role of negative affect in the development and persistence of CI in a general population. A general population sample aged 19 to 72years was examined in 2006-2008 and again in 2011-2012. Longitudinal data on CI were analysed with the purpose of examining baseline negative affect as a risk factor for having developed CI at 5-year follow-up and for reporting persistent CI. Participants were classified as reporting no signs of CI, having symptoms of CI and as being a likely CI case based on self-reported reactions to 11 common chemical exposures, symptoms related to chemical exposures and daily life adjustments attributed to reactions when exposed to chemicals. A total of 69.4% of the participants who had reported CI at baseline also reported CI at follow-up. In participants with no baseline CI, 1...
Circulation. Cardiovascular genetics, Jan 24, 2015
-There are several well-established lifestyle factors influencing dyslipidemia and currently, 157... more -There are several well-established lifestyle factors influencing dyslipidemia and currently, 157 genetic susceptibility loci have been reported to be associated with serum lipid levels at genome-wide statistical significance. However, the interplay between lifestyle risk factors and these susceptibility loci has not been fully elucidated. We tested if genetic risk scores (GRS) of lipid-associated SNPs associate with fasting serum lipid traits and if the effects are modulated by lifestyle factors or estimates of metabolic health. -The SNPs were genotyped in two Danish cohorts: Inter99 (n=5,961) for discovery analyses and Health2006 (n=2,565) for replication. Based on published effect sizes of SNPs associated with circulating fasting levels of total cholesterol, LDL-cholesterol, HDL-cholesterol or triglyceride, four weighted GRS (wGRS) were constructed. In a cross-sectional design, we investigated if the effect of these wGRSs on lipid levels were modulated by diet, alcohol consumption, physical activity and smoking or the individual metabolic health status as estimated from BMI, waist circumference and insulin resistance assessed using HOMA-IR. All four lipid wGRSs associated strongly with their respective trait (from P=3.3×10(-69) to P=1.1×10(-123)). We found interactions between the triglyceride wGRS and BMI and waist circumference on fasting triglyceride levels in Inter99 and replicated these findings in Health2006 (Pinteraction=9.8×10(-5) and 2.0×10(-5), respectively in combined analysis). -Our findings suggest that individuals who are obese may be more susceptible to the cumulative genetic burden of triglyceride SNPs. Therefore, it is suggested that especially these genetically at-risk individuals may benefit more from targeted interventions aiming at obesity prevention.
European journal of preventive cardiology, Jan 3, 2014
Excessive salt intake causes increased blood pressure which is considered the leading risk for pr... more Excessive salt intake causes increased blood pressure which is considered the leading risk for premature death. One major challenge when evaluating associations between daily salt intake and markers of non-communicable diseases is that a high daily salt intake correlates with obesity, which is also a well described risk factor for poor cardiometabolic outcome. The aim of this study was to evaluate the relationship of estimated daily salt intake with blood pressure and blood lipids and to investigate the effect of taking different measures of obesity into account. We included 3294 men and women aged 18-69 years from a general population based study in Copenhagen, Denmark. Estimated 24-hour sodium excretion was calculated by measurements of creatinine and sodium concentration in spot urine in combination with information of sex, age, height and weight. The relations of estimated 24-hour sodium excretion with blood pressure and blood lipids were evaluated by linear regression models. T...
The aim of this paper was to identify the extent of socioeconomic inequality in participation at ... more The aim of this paper was to identify the extent of socioeconomic inequality in participation at baseline and follow-up visits. The Inter99 study is a randomized intervention with the aim of investigating the effects of an individualized lifestyle consultation on ischaemic heart disease (IHD). The study comprised 61,301 persons of which 13,016 were assigned to the intervention group. The rest formed the control group. All those in the intervention group were invited to participate in health examinations, risk assessments, and lifestyle consultations. Participants at high risk of IHD were invited to follow-up visits after 1, 3, and 5 years. Data on five socioeconomic factors were retrieved from nationwide registers. For each socioeconomic factor we estimated the relative risks and relative index of inequality of participation at the baseline visit and among high-risk participants at follow-up visits. In addition, we conducted analyses of trends in socioeconomic inequality in participation across follow-up visits. Participation rates were 53% at baseline and 61-65% at the three follow-up visits. There was strong socioeconomic inequality in participation at baseline, with increasing probability of participation found with increasing level of socioeconomic position. This was smaller at follow-up visits. Except for education and housing tenure, there was an increase in socioeconomic inequality in participation across follow-up visits. We found strong socioeconomic inequality in participation at baseline and follow-up visits. Effort should be made to increase participation in individualized lifestyle interventions among persons of low socioeconomic position. Otherwise, the consequence may be increased socioeconomic inequality in IHD.
Common diseases like essential hypertension or diabetes mellitus are complex as they are polygeni... more Common diseases like essential hypertension or diabetes mellitus are complex as they are polygenic in nature, such that each genetic variation only has a small influence on the disease. Genes operates in integrated networks providing the blue-print for all biological processes and conditional of the complex genotype determines the state and dynamics of any trait, which may be modified to various extent by non-genetic factors. Thus, diseases are heterogenous ensembles of conditions with a common endpoint. Numerous studies have been performed to define genes of importance for a trait or disease, but only a few genes with small effect have been identified. The major reasons for this modest progress is the unresolved heterogeneity of the regulation of blood pressure and the shortcomings of the prevailing monogenic approach to capture genetic effects in a polygenic condition. Here, a two-step procedure is presented in which physiological heterogeneity is disentangled and genetic effects ...
Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impac... more Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on allcause mortality in people aged Z60 years.
Alcoholism: Clinical and Experimental Research, 2008
Background: A number of studies have shown that self-reported alcohol intake is positively associ... more Background: A number of studies have shown that self-reported alcohol intake is positively associated with total serum immunoglobin E (IgE) levels. The purpose of the present study was to investigate the association of self-reported alcohol consumption and different biomarkers of alcohol exposure to total serum IgE levels in a general adult population.
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Papers by Allan Linneberg