ORCID Profile
0000-0001-9453-2830
Current Organisations
Aalborg Universitet
,
Center for Clinical Research and Prevention
,
IT University of Copenhagen
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Publisher: Springer Science and Business Media LLC
Date: 24-04-2014
Publisher: Elsevier BV
Date: 12-2019
Publisher: Springer Science and Business Media LLC
Date: 14-12-2008
DOI: 10.1038/NG.274
Abstract: Obesity results from the interaction of genetic and environmental factors. To search for sequence variants that affect variation in two common measures of obesity, weight and body mass index (BMI), both of which are highly heritable, we performed a genome-wide association (GWA) study with 305,846 SNPs typed in 25,344 Icelandic, 2,998 Dutch, 1,890 European Americans and 1,160 African American subjects and combined the results with previously published results from the Diabetes Genetics Initiative (DGI) on 3,024 Scandinavians. We selected 43 variants in 19 regions for follow-up in 5,586 Danish in iduals and compared the results to a genome-wide study on obesity-related traits from the GIANT consortium. In total, 29 variants, some correlated, in 11 chromosomal regions reached a genome-wide significance threshold of P < 1.6 x 10(-7). This includes previously identified variants close to or in the FTO, MC4R, BDNF and SH2B1 genes, in addition to variants at seven loci not previously connected with obesity.
Publisher: American Diabetes Association
Date: 03-2009
DOI: 10.2337/DC08-0867
Abstract: OBJECTIVE—Bimodality in the distribution of glucose has been used to define the cut point for the diagnosis of diabetes. Previous studies on bimodality have primarily been in populations with a high prevalence of type 2 diabetes, including one study in a white Caucasian population. All studies included participants with known diabetes. The aim of this study was to assess whether a bimodal structure is a general phenomenon in fasting plasma glucose (FPG) and 2-h plasma glucose that is useful for deriving a common cut point for diabetes in populations of different origin, both including and excluding known diabetes. RESEARCH DESIGN AND METHODS—The Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project is an international collaboration pooling surveys from all continents. These studies include surveys in which plasma glucose was measured during an oral glucose tolerance test in total, 43 studies (135,383 participants) from 27 countries were included. A mixture of two normal distributions was fitted to plasma glucose levels, and a cut point for normal glycemia was estimated as their intersection. In populations with a biologically meaningful cut point, bimodality was tested for significance. RESULTS—Distributions of FPG and 2-h plasma glucose did not, in general, produce bimodal structures useful for deriving cut points for diabetes. When present, the cut points produced were inconsistent over geographical regions. CONCLUSIONS—Deriving cut points for normal glycemia from distributions of FPG and 2-h plasma glucose does not appear to be suitable for defining diagnostic cut points for diabetes.
Publisher: Massachusetts Medical Society
Date: 04-10-2012
Publisher: Oxford University Press (OUP)
Date: 14-08-2013
DOI: 10.1093/HMG/DDT399
Abstract: Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic in iduals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP [rs791595 risk allele = A risk allele frequency (RAF) = 0.080 P = 2.55 × 10(-13) odds ratio (OR) = 1.17], GPSM1 [rs11787792 risk allele = A RAF = 0.874 P = 1.74 × 10(-10) OR = 1.15] and SLC16A13 (rs312457 risk allele = G RAF = 0.078 P = 7.69 × 10(-13) OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.
Publisher: Public Library of Science (PLoS)
Date: 29-06-2016
Publisher: American Medical Association (AMA)
Date: 22-07-2009
Publisher: Elsevier BV
Date: 2010
Publisher: Elsevier BV
Date: 09-2011
Publisher: Springer Science and Business Media LLC
Date: 11-12-2011
DOI: 10.1038/NG.1019
Publisher: Oxford University Press (OUP)
Date: 23-07-2012
DOI: 10.1093/IJE/DYS086
Publisher: Oxford University Press (OUP)
Date: 03-05-2010
DOI: 10.1093/IJE/DYQ063
Publisher: Massachusetts Medical Society
Date: 27-06-2019
Publisher: Public Library of Science (PLoS)
Date: 15-09-2011
Publisher: Public Library of Science (PLoS)
Date: 31-10-2013
Publisher: Elsevier BV
Date: 03-2009
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.AMEPRE.2014.06.020
Abstract: Sedentary behavior is regarded as a distinct risk factor for cardiometabolic morbidity and mortality, but knowledge of the efficacy of interventions targeting reductions in sedentary behavior is limited. To investigate the effect of an in idualized face-to-face motivational counseling intervention aimed at reducing sitting time. A randomized, controlled, observer-blinded, community-based trial with two parallel groups using open-end randomization with 1:1 allocation. A total of 166 sedentary adults were consecutively recruited from the population-based Health2010 Study. Participants were randomized to a control (usual lifestyle) or intervention group with four in idual theory-based counseling sessions. Objectively measured overall sitting time (ActivPAL 3TM, 7 days) secondary measures were breaks in sitting time, anthropometric measures, and cardiometabolic biomarkers, assessed at baseline and after 6 months. Data were collected in 2010-2012 and analyzed in 2013-2014 using repeated measures multiple regression analyses. Ninety-three participants were randomized to the intervention group and 73 to the control group, and 149 completed the study. The intervention group had a mean sitting time decrease of -0.27 hours/day, corresponding to 2.9% of baseline sitting time (hours/day) the control group increased mean sitting time by 0.06 hours/day. The between-group difference in change, -0.32 hours/day (95% CI=-0.87, 0.24, p=0.26), was not statistically significant. Significant differences in change in fasting serum insulin of -5.9 pmol/L (95% CI=-11.4, -0.5, p=0.03) homeostasis model assessment-estimated insulin resistance of -0.28 (95% CI=-0.53, -0.03, p=0.03) and waist circumference of -1.42 cm (95% CI=-2.54, -0.29, p=0.01) were observed in favor of the intervention group. Although the observed decrease in sitting time was not significant, a community-based, in idually tailored, theory-based intervention program aimed at reducing sitting time may be effective for increasing standing and improving cardiometabolic health in sedentary adults. This study is registered at Clinicaltrials.gov (NCT00289237).
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NCOMMS10495
Abstract: To increase our understanding of the genetic basis of adiposity and its links to cardiometabolic disease risk, we conducted a genome-wide association meta-analysis of body fat percentage (BF%) in up to 100,716 in iduals. Twelve loci reached genome-wide significance ( P × 10 −8 ), of which eight were previously associated with increased overall adiposity (BMI, BF%) and four (in or near COBLL1/GRB14 , IGF2BP1 , PLA2G6 , CRTC1 ) were novel associations with BF%. Seven loci showed a larger effect on BF% than on BMI, suggestive of a primary association with adiposity, while five loci showed larger effects on BMI than on BF%, suggesting association with both fat and lean mass. In particular, the loci more strongly associated with BF% showed distinct cross-phenotype association signatures with a range of cardiometabolic traits revealing new insights in the link between adiposity and disease risk.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-04-2022
Abstract: Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood. In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all‐cause mortality in 108 363 in iduals (median age, 46.0 years 48.2% men) free of MI and AF at baseline from 6 European population‐based cohorts. During a maximum follow‐up of 10.0 years, 3558 (3.3%) in iduals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) in iduals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was % for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68 95% CI, 1.03–2.74) and subsequent AF after MI (HR, 1.75 95% CI, 1.31–2.34) both significantly increased overall mortality risk. We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.
Publisher: Springer Science and Business Media LLC
Date: 02-2016
DOI: 10.1038/NCOMMS10494
Abstract: Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin ( LEP ) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 in iduals and followed up loci reaching P −6 in 19,979 additional in iduals. We identify five loci robustly associated ( P × 10 −8 ) with leptin levels in/near LEP , SLC32A1 , GCKR , CCNL1 and FTO . Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin , a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
Publisher: Springer Science and Business Media LLC
Date: 02-2017
DOI: 10.1038/NATURE21039
Publisher: Springer Science and Business Media LLC
Date: 12-11-2005
DOI: 10.1007/S00125-005-0049-7
Abstract: The 825C>T polymorphism in the gene encoding the G protein beta3 subunit (GNB3) causes enhanced G protein activation and increased in vitro cell proliferation. This polymorphism is also repeatedly associated with an increased risk of hypertension and has been studied in relation to obesity with ergent results. Only a few association studies have investigated whether this polymorphism is related to type 2 diabetes or the metabolic syndrome. We estimated the impact of the GNB3 825C>T polymorphism in relatively large-scale association studies of common phenotypes of the metabolic syndrome. The GNB3 825C>T polymorphism was genotyped in 7,518 white Danish subjects using mass spectrometry analysis of PCR products. Case-control studies were undertaken for obesity, hypertension, type 2 diabetes and the metabolic syndrome, and a meta-analysis including data from the present study and previous studies of hypertension was performed. Quantitative trait studies of metabolic variables were carried out in 4,387 glucose-tolerant subjects. We observed minor differences in 825C>T genotype distributions for type 2 diabetes (CC/CT/TT 49/41/10% (control) vs 46/46/9% (cases), respectively, p=0.007) however, after correction for multiple testing, these were not statistically significant. No association was found with hypertension, obesity or the metabolic syndrome. Curiously, the T allele was associated with nominally lower systolic and diastolic blood pressure levels-a finding in contrast with most previous studies-but not with other metabolic variables. Meta-analysis demonstrated a high degree of heterogeneity between study populations of different ethnic origin. Although there was a tendency towards an increased risk of hypertension among 825T allele carriers, this was not statistically significant. The present study suggests no major involvement of the GNB3 825C>T polymorphism in components of the metabolic syndrome.
Publisher: Massachusetts Medical Society
Date: 03-03-2011
Publisher: Public Library of Science (PLoS)
Date: 30-07-2013
Publisher: Springer Science and Business Media LLC
Date: 03-06-2019
DOI: 10.1038/S41588-019-0447-2
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Springer Science and Business Media LLC
Date: 02-12-2012
DOI: 10.1038/NG.2477
Publisher: Springer Science and Business Media LLC
Date: 25-09-2013
Publisher: American Medical Association (AMA)
Date: 12-2019
Publisher: Oxford University Press (OUP)
Date: 19-03-2018
DOI: 10.1093/IJE/DYY016
Publisher: Oxford University Press (OUP)
Date: 22-11-2018
Publisher: Oxford University Press (OUP)
Date: 23-04-2014
DOI: 10.1093/HMG/DDU183
Publisher: Oxford University Press (OUP)
Date: 18-11-2019
Abstract: Limited evidence is available on the temporal relationship between atrial fibrillation (AF) and ischaemic stroke and their impact on mortality in the community. We sought to understand the temporal relationship of AF and ischaemic stroke and to determine the sequence of disease onset in relation to mortality. Across five prospective community cohorts of the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project we assessed baseline cardiovascular risk factors in 100 132 in iduals, median age 46.1 (25th–75th percentile 35.8–57.5) years, 48.4% men. We followed them for incident ischaemic stroke and AF and determined the relation of subsequent disease diagnosis with overall mortality. Over a median follow-up of 16.1 years, N = 4555 in iduals were diagnosed solely with AF, N = 2269 had an ischaemic stroke but no AF diagnosed, and N = 898 developed both, ischaemic stroke and AF. Temporal relationships showed a clustering of diagnosis of both diseases within the years around the diagnosis of the other disease. In multivariable-adjusted Cox regression analyses with time-dependent covariates subsequent diagnosis of AF after ischaemic stroke was associated with increased mortality [hazard ratio (HR) 4.05, 95% confidence interval (CI) 2.17–7.54 P & 0.001] which was also apparent when ischaemic stroke followed after the diagnosis of AF (HR 3.08, 95% CI 1.90–5.00 P & 0.001). The temporal relations of ischaemic stroke and AF appear to be bidirectional. Ischaemic stroke may precede detection of AF by years. The subsequent diagnosis of both diseases significantly increases mortality risk. Future research needs to investigate the common underlying systemic disease processes.
Publisher: Public Library of Science (PLoS)
Date: 10-03-2011
Publisher: Springer Science and Business Media LLC
Date: 18-09-2007
DOI: 10.1007/S10654-007-9165-7
Abstract: Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of in idual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.
Publisher: Public Library of Science (PLoS)
Date: 07-08-2014
Publisher: Oxford University Press (OUP)
Date: 22-12-2013
DOI: 10.1093/AJE/KWT298
Publisher: Springer Science and Business Media LLC
Date: 22-05-2017
DOI: 10.1038/S41598-017-01977-W
Abstract: Observational studies on smoking and risk of hay fever and asthma have shown inconsistent results. However, observational studies may be biased by confounding and reverse causation. Mendelian randomization uses genetic variants as markers of exposures to examine causal effects. We examined the causal effect of smoking on hay fever and asthma by using the smoking-associated single nucleotide polymorphism (SNP) rs16969968/rs1051730. We included 231,020 participants from 22 population-based studies. Observational analyses showed that current vs never smokers had lower risk of hay fever (odds ratio (OR) = 0·68, 95% confidence interval (CI): 0·61, 0·76 P 0·001) and allergic sensitization (OR = 0·74, 95% CI: 0·64, 0·86 P 0·001), but similar asthma risk (OR = 1·00, 95% CI: 0·91, 1·09 P = 0·967). Mendelian randomization analyses in current smokers showed a slightly lower risk of hay fever (OR = 0·958, 95% CI: 0·920, 0·998 P = 0·041), a lower risk of allergic sensitization (OR = 0·92, 95% CI: 0·84, 1·02 P = 0·117), but higher risk of asthma (OR = 1·06, 95% CI: 1·01, 1·11 P = 0·020) per smoking-increasing allele. Our results suggest that smoking may be causally related to a higher risk of asthma and a slightly lower risk of hay fever. However, the adverse events associated with smoking limit its clinical significance.
Publisher: Springer Science and Business Media LLC
Date: 23-11-2016
DOI: 10.1038/NCOMMS13357
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 % 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.
Publisher: American Diabetes Association
Date: 16-04-2013
DOI: 10.2337/DB12-1077
Abstract: We performed a genome-wide association study (GWAS) and a multistage meta-analysis of type 2 diabetes (T2D) in Punjabi Sikhs from India. Our discovery GWAS in 1,616 in iduals (842 case subjects) was followed by in silico replication of the top 513 independent single nucleotide polymorphisms (SNPs) (P & 10−3) in Punjabi Sikhs (n = 2,819 801 case subjects). We further replicated 66 SNPs (P & 10−4) through genotyping in a Punjabi Sikh s le (n = 2,894 1,711 case subjects). On combined meta-analysis in Sikh populations (n = 7,329 3,354 case subjects), we identified a novel locus in association with T2D at 13q12 represented by a directly genotyped intronic SNP (rs9552911, P = 1.82 × 10−8) in the SGCG gene. Next, we undertook in silico replication (stage 2b) of the top 513 signals (P & 10−3) in 29,157 non-Sikh South Asians (10,971 case subjects) and de novo genotyping of up to 31 top signals (P & 10−4) in 10,817 South Asians (5,157 case subjects) (stage 3b). In combined South Asian meta-analysis, we observed six suggestive associations (P & 10−5 to & 10−7), including SNPs at HMG1L1/CTCFL, PLXNA4, SCAP, and chr5p11. Further evaluation of 31 top SNPs in 33,707 East Asians (16,746 case subjects) (stage 3c) and 47,117 Europeans (8,130 case subjects) (stage 3d), and joint meta-analysis of 128,127 in iduals (44,358 case subjects) from 27 multiethnic studies, did not reveal any additional loci nor was there any evidence of replication for the new variant. Our findings provide new evidence on the presence of a population-specific signal in relation to T2D, which may provide additional insights into T2D pathogenesis.
Publisher: Public Library of Science (PLoS)
Date: 10-2015
Publisher: Springer Science and Business Media LLC
Date: 27-06-2010
DOI: 10.1038/NG.609
Publisher: Elsevier BV
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 10-08-2011
Abstract: To investigate the relationship between body mass index (BMI) and mortality from various causes. Data of 72,947 European men and 62,798 women aged 24-99 years at baseline were collaboratively analyzed. Both absolute and relative mortality risks were estimated within each BMI categories. The hazard ratio was estimated using Cox regression analysis adjusting for age, cohort and smoking status. Over a median follow-up of 16.8 years, 29,071 participants died, 13,502 from cardiovascular disease (CVD) and 8748 from cancers of all types. All-cause and cancer mortality showed a U-shaped relationship: decreased first, leveled off, and then increased with increasing BMI with the lowest mortality risk approximately between 23.0 and 28.0 kg/m(2) of BMI in men and 21.0 and 28.0 kg/m(2) in women. The U-shaped relationship held for all-cause mortality but disappeared for cancer mortality among non-smokers. The CVD mortality was constant until a BMI of approximately 28.0 kg/m(2) and then increased gradually in both men and women, which was independent of age, cohort and smoking status. A U-shaped relationship of BMI with all-cause mortality but a graded relationship with CVD mortality at BMI >28.0 kg/m(2) was detected. The relationship between cancer mortality and BMI largely depended on smoking status, and need to be further investigated with site-specific cancers.
Publisher: Springer Science and Business Media LLC
Date: 06-01-2008
DOI: 10.1038/NG.72
Abstract: Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our s les, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.
Publisher: Informa UK Limited
Date: 07-06-2010
DOI: 10.3109/14017431.2010.483612
Abstract: To develop a cardiovascular risk model simulating different clinical settings using a staged approach. Using data from 27,477 men and women from the Norwegian Tromsø Study in 1986-1987 and 1994-1995, Cox regression models for either myocardial infarction (MI) or stroke combined with a similar model for the competing event a risk model that assess ten-year risk of MI and stroke was developed. Explanatory variables (questions, simple examinations and blood s les) were added gradually. The model was validated using Hosmer-Lemeshow test, the Brier score, c-index, integrated discrimination improvement (IDI) and Net Reclassification Improvement (NRI). In total, 1,298 events of MI and 769 events of stroke were registered. For MI the model showed excellent discrimination in each step with c-index from 0.833 to 0.946. For stroke the c-index ranged between 0.817 and 0.898. IDI showed significant increases in discrimination. The Brier scores and goodness of fit test showed well calibrated models in all steps for all sex- and end-point specific models (p>0.05). Although the predictive and discriminative ability of the models increased with each step, even the simplest model containing only data from questions or blood s les alone yielded valid estimates of cardiovascular risk.
Publisher: American Medical Association (AMA)
Date: 11-11-2009
Publisher: Springer Science and Business Media LLC
Date: 26-04-2007
DOI: 10.1038/NG2043
Abstract: We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in in iduals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and in iduals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.
Publisher: Elsevier BV
Date: 07-2018
Publisher: Elsevier BV
Date: 06-2010
Publisher: Wiley
Date: 09-09-2011
DOI: 10.1002/SIM.4362
Publisher: Springer Science and Business Media LLC
Date: 05-2019
Publisher: Public Library of Science (PLoS)
Date: 10-05-2012
Publisher: Springer Science and Business Media LLC
Date: 22-12-2017
Publisher: Springer Science and Business Media LLC
Date: 06-06-2006
Abstract: The estrogen-related receptor alpha (ERRalpha or NR3B1) is a transcription factor from the nuclear receptor super-family, group III. The gene encoding ERRalpha (ESRRA) is located on chromosome 11q13, a region showing genetic linkage to body mass index and fat percentage. Through interaction with the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), ERRalpha regulates key enzymes involved in the beta-oxidation of fatty acids. By screening 48 overweight or obese subjects for variants in the exons, exon-intron boundaries and 1000 base pairs (bp) of the promoter region of ESRRA using bi-directional nucleotide sequencing, we identified seven variants. Four rare variants had minor allele frequencies (MAF) below 1%: Pro369Pro, Gly406Asp, 3'UTR+418G>A, 3'UTR+505C>A. Two single-nucleotide polymorphisms, Pro116Pro and IVS6+65C>T (MAF 15%), were in complete linkage disequilibrium (LD) (r (2)=1). We also confirmed the presence of a reported 23 bp microsatellite repeat (ESRRA23). The Pro116Pro and ESRRA23 variants were not associated with obesity, type 2 diabetes or related phenotypes in a large population-based study of 6365 Danish whites. The two variants were examined for interactions with variants in the peroxisome proliferator-activated receptor-gamma coactivator-1alpha and -beta however, no evidence of epistatic effects between the variants was demonstrated. The ESRRA23 and Pro116Pro variants of the gene encoding ERRalpha are not associated with obesity, type 2 diabetes or related quantitative traits in the examined Danish whites.
Publisher: Springer Science and Business Media LLC
Date: 19-12-2017
Abstract: To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European in iduals and exome sequencing of 12,940 in iduals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1–5%) non-coding variants in the whole-genome sequenced in iduals and 99.7% of low-frequency coding variants in the whole-exome sequenced in iduals. Each variant was tested for association with T2D in the sequenced in iduals, and, to increase power, most were tested in larger numbers of in iduals ( % of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
No related grants have been discovered for Torben Jørgensen.