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Search Results: 1 - 10 of 309724 matches for " B?rge G. Nordestgaard equal contributor "
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The Effect of Elevated Body Mass Index on Ischemic Heart Disease Risk: Causal Estimates from a Mendelian Randomisation Approach
Brge G. Nordestgaard equal contributor ,Tom M. Palmer equal contributor,Marianne Benn,Jeppe Zacho,Anne Tybj?rg-Hansen,George Davey Smith,Nicholas J. Timpson
PLOS Medicine , 2012, DOI: 10.1371/journal.pmed.1001212
Abstract: Background Adiposity, assessed as elevated body mass index (BMI), is associated with increased risk of ischemic heart disease (IHD); however, whether this is causal is unknown. We tested the hypothesis that positive observational associations between BMI and IHD are causal. Methods and Findings In 75,627 individuals taken from two population-based and one case-control study in Copenhagen, we measured BMI, ascertained 11,056 IHD events, and genotyped FTO(rs9939609), MC4R(rs17782313), and TMEM18(rs6548238). Using genotypes as a combined allele score in instrumental variable analyses, the causal odds ratio (OR) between BMI and IHD was estimated and compared with observational estimates. The allele score-BMI and the allele score-IHD associations used to estimate the causal OR were also calculated individually. In observational analyses the OR for IHD was 1.26 (95% CI 1.19–1.34) for every 4 kg/m2 increase in BMI. A one-unit allele score increase associated with a 0.28 kg/m2 (95 CI% 0.20–0.36) increase in BMI and an OR for IHD of 1.03 (95% CI 1.01–1.05) (corresponding to an average 1.68 kg/m2 BMI increase and 18% increase in the odds of IHD for those carrying all six BMI increasing alleles). In instrumental variable analysis using the same allele score the causal IHD OR for a 4 kg/m2 increase in BMI was 1.52 (95% CI 1.12–2.05). Conclusions For every 4 kg/m2 increase in BMI, observational estimates suggested a 26% increase in odds for IHD while causal estimates suggested a 52% increase. These data add evidence to support a causal link between increased BMI and IHD risk, though the mechanism may ultimately be through intermediate factors like hypertension, dyslipidemia, and type 2 diabetes. This work has important policy implications for public health, given the continuous nature of the BMI-IHD association and the modifiable nature of BMI. This analysis demonstrates the value of observational studies and their ability to provide unbiased results through inclusion of genetic data avoiding confounding, reverse causation, and bias. Please see later in the article for the Editors' Summary
Fine-Mapping the HOXB Region Detects Common Variants Tagging a Rare Coding Allele: Evidence for Synthetic Association in Prostate Cancer
Edward J. Saunders,Tokhir Dadaev,Daniel A. Leongamornlert,Sarah Jugurnauth-Little,Malgorzata Tymrakiewicz,Fredrik Wiklund,Ali Amin Al Olama,Sara Benlloch,David E. Neal equal contributor,Freddie C. Hamdy equal contributor,Jenny L. Donovan equal contributor,Graham G. Giles equal contributor,Gianluca Severi equal contributor,Henrik Gronberg equal contributor,Markus Aly equal contributor,Christopher A. Haiman equal contributor,Fredrick Schumacher equal contributor,Brian E. Henderson equal contributor,Sara Lindstrom equal contributor,Peter Kraft equal contributor,David J. Hunter equal contributor,Susan Gapstur equal contributor,Stephen Chanock equal contributor,Sonja I. Berndt equal contributor,Demetrius Albanes equal contributor,Gerald Andriole equal contributor,Johanna Schleutker equal contributor,Maren Weischer equal contributor,Brge G. Nordestgaard equal contributor,Federico Canzian equal contributor,Daniele Campa equal contributor,Elio Riboli equal contributor,Tim J. Key equal contributor,Ruth C. Travis equal contributor,Sue A. Ingles equal contributor,Esther M. John equal contributor,Richard B. Hayes equal contributor,Paul Pharoah equal contributor,Kay-Tee Khaw equal contributor,Janet L. Stanford equal contributor,Elaine A. Ostrander equal contributor,Lisa B. Signorello equal contributor,Stephen N. Thibodeau equal contributor,Daniel Schaid equal contributor,Christiane Maier equal contributor,Adam S. Kibel equal contributor,Cezary Cybulski equal contributor
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004129
Abstract: The HOXB13 gene has been implicated in prostate cancer (PrCa) susceptibility. We performed a high resolution fine-mapping analysis to comprehensively evaluate the association between common genetic variation across the HOXB genetic locus at 17q21 and PrCa risk. This involved genotyping 700 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of 3195 SNPs in 20,440 PrCa cases and 21,469 controls in The PRACTICAL consortium. We identified a cluster of highly correlated common variants situated within or closely upstream of HOXB13 that were significantly associated with PrCa risk, described by rs117576373 (OR 1.30, P = 2.62×10?14). Additional genotyping, conditional regression and haplotype analyses indicated that the newly identified common variants tag a rare, partially correlated coding variant in the HOXB13 gene (G84E, rs138213197), which has been identified recently as a moderate penetrance PrCa susceptibility allele. The potential for GWAS associations detected through common SNPs to be driven by rare causal variants with higher relative risks has long been proposed; however, to our knowledge this is the first experimental evidence for this phenomenon of synthetic association contributing to cancer susceptibility.
Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias
Robert Clarke equal contributor ,Derrick A. Bennett equal contributor,Sarah Parish equal contributor,Petra Verhoef,Mariska D?tsch-Klerk,Mark Lathrop,Peng Xu,Brge G. Nordestgaard,Hilma Holm,Jemma C. Hopewell,Danish Saleheen,Toshihiro Tanaka,Sonia S. Anand,John C. Chambers,Marcus E. Kleber,Willem H. Ouwehand,Yoshiji Yamada,Clara Elbers,Bas Peters,Alexandre F. R. Stewart,Muredach M. Reilly,Barbara Thorand,Salim Yusuf,James C. Engert,Themistocles L. Assimes,Jaspal Kooner,John Danesh,Hugh Watkins,Nilesh J. Samani,Rory Collins equal contributor,Richard Peto equal contributor,for the MTHFR Studies Collaborative Group
PLOS Medicine , 2012, DOI: 10.1371/journal.pmed.1001177
Abstract: Background Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality. Methods and Findings Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09–1.28) in the 72 smaller ones (total 15,498 cases). Conclusions The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems. Please see later in the article for the Editors' Summary
GUESS-ing Polygenic Associations with Multiple Phenotypes Using a GPU-Based Evolutionary Stochastic Search Algorithm
Leonardo Bottolo equal contributor ,Marc Chadeau-Hyam equal contributor,David I. Hastie,Tanja Zeller,Benoit Liquet,Paul Newcombe,Loic Yengo,Philipp S. Wild,Arne Schillert,Andreas Ziegler,Sune F. Nielsen,Adam S. Butterworth,Weang Kee Ho,Rapha?le Castagné,Thomas Munzel,David Tregouet,Mario Falchi,Fran?ois Cambien,Brge G. Nordestgaard,Fredéric Fumeron,Anne Tybj?rg-Hansen,Philippe Froguel,John Danesh,Enrico Petretto,Stefan Blankenberg,Laurence Tiret,Sylvia Richardson
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003657
Abstract: Genome-wide association studies (GWAS) yielded significant advances in defining the genetic architecture of complex traits and disease. Still, a major hurdle of GWAS is narrowing down multiple genetic associations to a few causal variants for functional studies. This becomes critical in multi-phenotype GWAS where detection and interpretability of complex SNP(s)-trait(s) associations are complicated by complex Linkage Disequilibrium patterns between SNPs and correlation between traits. Here we propose a computationally efficient algorithm (GUESS) to explore complex genetic-association models and maximize genetic variant detection. We integrated our algorithm with a new Bayesian strategy for multi-phenotype analysis to identify the specific contribution of each SNP to different trait combinations and study genetic regulation of lipid metabolism in the Gutenberg Health Study (GHS). Despite the relatively small size of GHS (n = 3,175), when compared with the largest published meta-GWAS (n>100,000), GUESS recovered most of the major associations and was better at refining multi-trait associations than alternative methods. Amongst the new findings provided by GUESS, we revealed a strong association of SORT1 with TG-APOB and LIPC with TG-HDL phenotypic groups, which were overlooked in the larger meta-GWAS and not revealed by competing approaches, associations that we replicated in two independent cohorts. Moreover, we demonstrated the increased power of GUESS over alternative multi-phenotype approaches, both Bayesian and non-Bayesian, in a simulation study that mimics real-case scenarios. We showed that our parallel implementation based on Graphics Processing Units outperforms alternative multi-phenotype methods. Beyond multivariate modelling of multi-phenotypes, our Bayesian model employs a flexible hierarchical prior structure for genetic effects that adapts to any correlation structure of the predictors and increases the power to identify associated variants. This provides a powerful tool for the analysis of diverse genomic features, for instance including gene expression and exome sequencing data, where complex dependencies are present in the predictor space.
Causal and Synthetic Associations of Variants in the SERPINA Gene Cluster with Alpha1-antitrypsin Serum Levels
Gian Andri Thun,Medea Imboden equal contributor,Ilaria Ferrarotti equal contributor,Ashish Kumar,Ma'en Obeidat,Michele Zorzetto,Margot Haun,Ivan Curjuric,Alexessander Couto Alves,Victoria E. Jackson,Eva Albrecht,Janina S. Ried,Alexander Teumer,Lorna M. Lopez,Jennifer E. Huffman,Stefan Enroth,Yohan Bossé,Ke Hao,Wim Timens,Ulf Gyllensten,Ozren Polasek,James F. Wilson,Igor Rudan,Caroline Hayward,Andrew J. Sandford,Ian J. Deary,Beate Koch,Eva Reischl,Holger Schulz,Jennie Hui,Alan L. James,Thierry Rochat,Erich W. Russi,Marjo-Riitta Jarvelin,David P. Strachan,Ian P. Hall,Martin D. Tobin,Morten Dahl,Sune Fallgaard Nielsen,Brge G. Nordestgaard,Florian Kronenberg,Maurizio Luisetti,Nicole M. Probst-Hensch
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003585
Abstract: Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of β = ?0.068 g/L per minor allele (P = 1.20*10?12). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1–5%) variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z) variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001), as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57). Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397), associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population.
Genetic Predisposition to In Situ and Invasive Lobular Carcinoma of the Breast
Elinor Sawyer equal contributor ,Rebecca Roylance equal contributor,Christos Petridis,Mark N. Brook,Salpie Nowinski,Efterpi Papouli,Olivia Fletcher,Sarah Pinder,Andrew Hanby,Kelly Kohut,Patricia Gorman,Michele Caneppele,Julian Peto,Isabel dos Santos Silva,Nichola Johnson,Ruth Swann,Miriam Dwek,Katherine-Anne Perkins,Cheryl Gillett,Richard Houlston,Gillian Ross,Paolo De Ieso,Melissa C. Southey,John L. Hopper,Elena Provenzano,Carmel Apicella,Jelle Wesseling,Sten Cornelissen,Renske Keeman,Peter A. Fasching,Sebastian M. Jud,Arif B. Ekici,Matthias W. Beckmann,Michael J. Kerin,Federick Marme,Andreas Schneeweiss,Christof Sohn,Barbara Burwinkel,Pascal Guénel,Therese Truong,Pierre Laurent-Puig,Pierre Kerbrat,Stig E. Bojesen,Brge G. Nordestgaard,Sune F. Nielsen,Henrik Flyger,Roger L. Milne,Jose Ignacio Arias Perez,Primitiva Menéndez,Javier Benitez,Hermann Brenner,Aida Karina Dieffenbach,Volker Arndt,Christa Stegmaier,Alfons Meindl,Peter Lichtner,Rita K. Schmutzler,Magdalena Lochmann,Hiltrud Brauch,Hans-Peter Fischer,Yon-Dschun Ko,The GENICA Network ?,Heli Nevanlinna,Taru A. Muranen,Kristiina Aittom?ki,Carl Blomqvist,Natalia V. Bogdanova,Thilo D?rk,Annika Lindblom,Sara Margolin,Arto Mannermaa,Vesa Kataja,Veli-Matti Kosma,Jaana M. Hartikainen,Georgia Chenevix-Trench,kConFab Investigators ?,Diether Lambrechts,Caroline Weltens,Erik Van Limbergen,Sigrid Hatse,Jenny Chang-Claude,Anja Rudolph,Petra Seibold,Dieter Flesch-Janys,Paolo Radice,Paolo Peterlongo,Bernardo Bonanni,Sara Volorio
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004285
Abstract: Invasive lobular breast cancer (ILC) accounts for 10–15% of all invasive breast carcinomas. It is generally ER positive (ER+) and often associated with lobular carcinoma in situ (LCIS). Genome-wide association studies have identified more than 70 common polymorphisms that predispose to breast cancer, but these studies included predominantly ductal (IDC) carcinomas. To identify novel common polymorphisms that predispose to ILC and LCIS, we pooled data from 6,023 cases (5,622 ILC, 401 pure LCIS) and 34,271 controls from 36 studies genotyped using the iCOGS chip. Six novel SNPs most strongly associated with ILC/LCIS in the pooled analysis were genotyped in a further 516 lobular cases (482 ILC, 36 LCIS) and 1,467 controls. These analyses identified a lobular-specific SNP at 7q34 (rs11977670, OR (95%CI) for ILC = 1.13 (1.09–1.18), P = 6.0×10?10; P-het for ILC vs IDC ER+ tumors = 1.8×10?4). Of the 75 known breast cancer polymorphisms that were genotyped, 56 were associated with ILC and 15 with LCIS at P<0.05. Two SNPs showed significantly stronger associations for ILC than LCIS (rs2981579/10q26/FGFR2, P-het = 0.04 and rs889312/5q11/MAP3K1, P-het = 0.03); and two showed stronger associations for LCIS than ILC (rs6678914/1q32/LGR6, P-het = 0.001 and rs1752911/6q14, P-het = 0.04). In addition, seven of the 75 known loci showed significant differences between ER+ tumors with IDC and ILC histology, three of these showing stronger associations for ILC (rs11249433/1p11, rs2981579/10q26/FGFR2 and rs10995190/10q21/ZNF365) and four associated only with IDC (5p12/rs10941679; rs2588809/14q24/RAD51L1, rs6472903/8q21 and rs1550623/2q31/CDCA7). In conclusion, we have identified one novel lobular breast cancer specific predisposition polymorphism at 7q34, and shown for the first time that common breast cancer polymorphisms predispose to LCIS. We have shown that many of the ER+ breast cancer predisposition loci also predispose to ILC, although there is some heterogeneity between ER+ lobular and ER+ IDC tumors. These data provide evidence for overlapping, but distinct etiological pathways within ER+ breast cancer between morphological subtypes.
Markers of early disease and prognosis in COPD
Morten Dahl, B rge G Nordestgaard
International Journal of Chronic Obstructive Pulmonary Disease , 2009, DOI: http://dx.doi.org/10.2147/COPD.S3106
Abstract: rkers of early disease and prognosis in COPD Review (7452) Total Article Views Authors: Morten Dahl, B rge G Nordestgaard Published Date April 2009 Volume 2009:4 Pages 157 - 167 DOI: http://dx.doi.org/10.2147/COPD.S3106 Morten Dahl, B rge G Nordestgaard Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark Abstract: COPD is a complex disease with multiple pathological components, which we unfortunately tend to ignore when spirometry is used as the only method to evaluate the disorder. Additional measures are needed to allow a more complete and clinically relevant assessment of COPD. The earliest potential risk factors of disease in COPD are variations in the genetic background. Genetic variations are present from conception and can determine lifelong changes in enzyme activities and protein concentrations. In contrast, measurements in blood, sputum, exhaled breath, broncho-alveolar lavage, and lung biopsies may vary substantially over time. This review explores potential markers of early disease and prognosis in COPD by examining genetic markers in the α1-antitrypsin, cystic fibrosis transmembrane conductance regulator (CFTR), and MBL-2 genes, and by examining the biochemical markers fibrinogen and C-reactive protein (CRP), which correlate with degree of pulmonary inflammation during stable conditions of COPD. Chronic lung inflammation appears to contribute to the pathogenesis of COPD, and markers of this process have promising predictive value in COPD. To implement markers for COPD in clinical practice, besides those already established for the α1-antitrypsin gene, further research and validation studies are needed.
Markers of early disease and prognosis in COPD
Morten Dahl,Børge G Nordestgaard
International Journal of COPD , 2009,
Abstract: Morten Dahl, B rge G NordestgaardDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkAbstract: COPD is a complex disease with multiple pathological components, which we unfortunately tend to ignore when spirometry is used as the only method to evaluate the disorder. Additional measures are needed to allow a more complete and clinically relevant assessment of COPD. The earliest potential risk factors of disease in COPD are variations in the genetic background. Genetic variations are present from conception and can determine lifelong changes in enzyme activities and protein concentrations. In contrast, measurements in blood, sputum, exhaled breath, broncho-alveolar lavage, and lung biopsies may vary substantially over time. This review explores potential markers of early disease and prognosis in COPD by examining genetic markers in the α1-antitrypsin, cystic fibrosis transmembrane conductance regulator (CFTR), and MBL-2 genes, and by examining the biochemical markers fibrinogen and C-reactive protein (CRP), which correlate with degree of pulmonary inflammation during stable conditions of COPD. Chronic lung inflammation appears to contribute to the pathogenesis of COPD, and markers of this process have promising predictive value in COPD. To implement markers for COPD in clinical practice, besides those already established for the α1-antitrypsin gene, further research and validation studies are needed.Keywords: chronic obstructive pulmonary disease, biomarker, pathogenesis, prognosis, genetics
Telomere Shortening Unrelated to Smoking, Body Weight, Physical Activity, and Alcohol Intake: 4,576 General Population Individuals with Repeat Measurements 10 Years Apart
Maren Weischer,Stig E. Bojesen,Brge G. Nordestgaard
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004191
Abstract: Cross-sectional studies have associated short telomere length with smoking, body weight, physical activity, and possibly alcohol intake; however, whether these associations are due to confounding is unknown. We tested these hypotheses in 4,576 individuals from the general population cross-sectionally, and with repeat measurement of relative telomere length 10 years apart. We also tested whether change in telomere length is associated with mortality and morbidity in the general population. Relative telomere length was measured with quantitative polymerase chain reaction. Cross-sectionally at the first examination, short telomere length was associated with increased age (P for trend across quartiles = 3×10?77), current smoking (P = 8×10?3), increased body mass index (P = 7×10?14), physical inactivity (P = 4×10?17), but not with increased alcohol intake (P = 0.10). At the second examination 10 years later, 56% of participants had lost and 44% gained telomere length with a mean loss of 193 basepairs. Change in leukocyte telomere length during 10 years was associated inversely with baseline telomere length (P<1×10?300) and age at baseline (P = 1×10?27), but not with baseline or 10-year inter-observational tobacco consumption, body weight, physical activity, or alcohol intake. Prospectively during a further 10 years follow-up after the second examination, quartiles of telomere length change did not associate with risk of all-cause mortality, cancer, chronic obstructive pulmonary disease, diabetes mellitus, ischemic cerebrovascular disease, or ischemic heart disease. In conclusion, smoking, increased body weight, and physical inactivity were associated with short telomere length cross-sectionally, but not with telomere length change during 10 years observation, and alcohol intake was associated with neither. Also, change in telomere length did not associate prospectively with mortality or morbidity in the general population.
Heterozygosity for E292V in ABCA3, lung function and COPD in 64,000 individuals
B?kvad-Hansen Marie,Nordestgaard Brge G,Dahl Morten
Respiratory Research , 2012, DOI: 10.1186/1465-9921-13-67
Abstract: Background Mutations in ATP-binding-cassette-member A3 (ABCA3) are related to severe chronic lung disease in neonates and children, but frequency of chronic lung disease due to ABCA3 mutations in the general population is unknown. We tested the hypothesis that individuals heterozygous for ABCA3 mutations have reduced lung function and increased risk of COPD in the general population. Methods We screened 760 individuals with extreme pulmonary phenotypes and identified three novel (H86Y, A320T, A1086D) and four previously described mutations (E292V, P766S, S1262G, R1474W) in the ABCA3 gene. We genotyped the entire Copenhagen City Heart study (n = 10,604) to assess the clinical importance of these mutations. To validate our findings we genotyped an additional 54,395 individuals from the Copenhagen General Population Study. Results In the Copenhagen City Heart Study individuals heterozygous for E292V had 5% reduced FEV1 % predicted compared with noncarriers (t-test: p = 0.008), and an increased odds ratio for COPD of 1.9 (95% CI: 1.1-3.1). In contrast, the A1086D mutation was associated with increased FEV1 % predicted (p = 0.03). None of the other ABCA3 mutations associated with lung function or COPD risk in the Copenhagen City Heart Study. In the larger Copenhagen General Population Study, and in the two studies combined, E292V heterozygotes did not have reduced lung function or increased risk of COPD (p = 0.11-0.98), while this was the case for the positive controls, surfactant protein-B 121ins2 heterozygotes and α1-antitrypsin ZZ homozygotes. Conclusion Our results indicate that partially reduced ABCA3 activity due to E292V is not a major risk factor for reduced lung function and COPD in the general population. This is an important finding as 1.3% in the Danish population has partially reduced ABCA3 function due to E292V.
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