Genome-wide association meta-analysis identifies risk loci for abdominal aortic aneurysm and highlights PCSK9 as a therapeutic target

J. Pankow | D. Gudbjartsson | U. Thorsteinsdóttir | K. Stefánsson | V. Zuber | G. Thorleifsson | I. Surakka | H. Hólm | I. Kullo | F. Dudbridge | J. van Setten | A. Wanhainen | S. Damrauer | S. Ganesh | W. Hornsby | K. Hveem | J. V. van Herwaarden | A. Locke | S. W. van der Laan | L. Tsoi | B. Brumpton | J. Lindholt | Tanmoy Roychowdhury | B. Wolford | D. Klarin | R. Judy | M. Levin | J. Spin | D. Gill | A. Baras | J. Gudjonsson | M. Sabater-Lleal | C. Erikstrup | K. Banasik | A. Christensen | J. Eliason | K. Mani | E. Strauss | G. Oszkinis | C. Gellatly | L. M. Obel | Colwyn A. Headley | N. Tsao | P. Tsao | Alicia Deng | A. Deng | Jaume Dilmé | O. Peypoch | K. Iversen | A. Handa | Jonas B. Nielsen | G. Einarsson | S. Gretarsdottir | S. Ostrowski | I. H. Laursen | Laura Calsina Juscafresa | H. Bundgaard | Stephen Burgess | R. L. Jacobsen | Dawn M. Coleman | Frank M. Davis | Weihua Guan | Christopher P. Nelson | Y. E. Chen | H. Ullum | Gregory T. Jones | M. Ferreira | Marylyn D. Ritchie | Lars M. Rasmussen | Dadong Li | Jack W. Pattee | Todd L. Edwards | Nilesh J. Samani | Weihong Tang | Regent Lee | Nathan Pankratz | Jifeng Zhang | Nikolaj Eldrup | Minerva T. Garcia-Barrio | S. Brunak | Peter K. Henke | Ozan Dikilitas | Cristen J. Willer | Rachael Wasikowski | O. Pedersen | Katherine A. Gallagher | S. Verma | YaeHyun Rhee | Fred Shen | Sarah E. Graham | Ferran Pauls-Verges | Katie L. Saxby | Mercedes Camacho | Henrik H. Sillesen | Frank Nilesh J. Dudbridge Samani | Matt J. Bown | K. Saxby | M. Bown

[1]  M. Sweet,et al.  Histone deacetylase 7: a signalling hub controlling development, inflammation, metabolism and disease , 2022, The FEBS journal.

[2]  W. Spiering,et al.  Genetic variants associated with low-density lipoprotein cholesterol and systolic blood pressure and the risk of recurrent cardiovascular disease in patients with established vascular disease. , 2022, Atherosclerosis.

[3]  Seunggeun Lee,et al.  NETMAGE: A human disease phenotype map generator for the network-based visualization of phenome-wide association study results , 2022, GigaScience.

[4]  Christopher D. Brown,et al.  The power of genetic diversity in genome-wide association studies of lipids , 2021, Nature.

[5]  H. Stefánsson,et al.  Cohort profile: Copenhagen Hospital Biobank - Cardiovascular Disease Cohort (CHB-CVDC): Construction of a large-scale genetic cohort to facilitate a better understanding of heart diseases , 2021, BMJ Open.

[6]  P. Linsley,et al.  Pcsk9 Deletion Promotes Murine Nonalcoholic Steatohepatitis and Hepatic Carcinogenesis: Role of Cholesterol , 2021, Hepatology communications.

[7]  E. Gamazon,et al.  Mapping the proteo-genomic convergence of human diseases , 2021, Science.

[8]  P. Tsao,et al.  Regulatory variants in TCF7L2 are associated with thoracic aortic aneurysm. , 2021, American journal of human genetics.

[9]  Katherine A. Gallagher,et al.  Inhibition of macrophage histone demethylase JMJD3 protects against abdominal aortic aneurysms , 2021, The Journal of experimental medicine.

[10]  K. Eagle,et al.  Disclosure of clinically actionable genetic variants to thoracic aortic dissection biobank participants , 2021, BMC Medical Genomics.

[11]  P. Tsao,et al.  Prioritizing the Role of Major Lipoproteins and Subfractions as Risk Factors for Peripheral Artery Disease , 2021, medRxiv.

[12]  H. Stefánsson,et al.  Data Resource Profile: The Copenhagen Hospital Biobank (CHB). , 2020, International journal of epidemiology.

[13]  Yan V. Sun,et al.  Genetic Architecture of Abdominal Aortic Aneurysm in the Million Veteran Program , 2020, Circulation.

[14]  Jacob C. Ulirsch,et al.  Leveraging polygenic enrichments of gene features to predict genes underlying complex traits and diseases , 2020, Nature Genetics.

[15]  Valeriia Haberland,et al.  The MRC IEU OpenGWAS data infrastructure , 2020, bioRxiv.

[16]  H. Stefánsson,et al.  Genetic variability in the absorption of dietary sterols affects the risk of coronary artery disease , 2020, European heart journal.

[17]  M. Schermerhorn,et al.  Abdominal aortic aneurysm screening guidelines: United States Preventative Services Task Force and Society for Vascular Surgery. , 2020, Journal of vascular surgery.

[18]  M. Sheahan,et al.  Evaluating the Prevalence of Abdominal Aortic Aneurysms in the United States through a National Screening Database. , 2020, Journal of vascular surgery.

[19]  M. Sabater-Lleal,et al.  The TAGA Study: A Study of Factors Determining Aortic Diameter in Families at High Risk of Abdominal Aortic Aneurysm Reveal Two New Candidate Genes , 2020, Journal of clinical medicine.

[20]  S. Mirarab,et al.  Sequence Analysis , 2020, Encyclopedia of Bioinformatics and Computational Biology.

[21]  V. Zuber,et al.  High-throughput multivariable Mendelian randomization analysis prioritizes apolipoprotein B as key lipid risk factor for coronary artery disease , 2020, International journal of epidemiology.

[22]  Stephen Burgess,et al.  Selecting likely causal risk factors from high-throughput experiments using multivariable Mendelian randomization , 2020, Nature Communications.

[23]  Christopher D. Brown,et al.  The GTEx Consortium atlas of genetic regulatory effects across human tissues , 2019, Science.

[24]  G. Angelini,et al.  Author Correction: WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling , 2019, Nature Communications.

[25]  H. Ullum,et al.  DBDS Genomic Cohort, a prospective and comprehensive resource for integrative and temporal analysis of genetic, environmental and lifestyle factors affecting health of blood donors , 2019, BMJ Open.

[26]  Mark R. Hurle,et al.  Phenome-wide Mendelian randomization mapping the influence of the plasma proteome on complex diseases , 2019, bioRxiv.

[27]  Stephen Burgess,et al.  A fast and efficient colocalization algorithm for identifying shared genetic risk factors across multiple traits , 2019, Nature Communications.

[28]  Gregory T. Jones,et al.  Genetics of Thoracic and Abdominal Aortic Diseases. , 2019, Circulation research.

[29]  John P. Rice,et al.  Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use , 2018, Nature Genetics.

[30]  Matthew S. Lebo,et al.  The eMERGE genotype set of 83,717 subjects imputed to ~40 million variants genome wide and association with the herpes zoster medical record phenotype , 2018, Genetic epidemiology.

[31]  Tanya M. Teslovich,et al.  Genetics of Blood Lipids Among ~300,000 Multi-Ethnic Participants of the Million Veteran Program , 2018, Nature Genetics.

[32]  Andrew D. Johnson,et al.  Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits , 2018, Nature Genetics.

[33]  Yang Ni,et al.  Polygenic prediction via Bayesian regression and continuous shrinkage priors , 2018, Nature Communications.

[34]  M. Mittleman,et al.  Statin therapy is associated with higher long‐term but not perioperative survival after abdominal aortic aneurysm repair , 2018, Journal of vascular surgery.

[35]  A. F. Scott,et al.  Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection. , 2018, Journal of the American College of Cardiology.

[36]  G. Davey Smith,et al.  Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians , 2018, British Medical Journal.

[37]  Valeriia Haberland,et al.  The MR-Base platform supports systematic causal inference across the human phenome , 2018, eLife.

[38]  Jia Gu,et al.  fastp: an ultra-fast all-in-one FASTQ preprocessor , 2018, bioRxiv.

[39]  N. Samani,et al.  Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm , 2017, JAMA cardiology.

[40]  Chunlei Liu,et al.  ClinVar: improving access to variant interpretations and supporting evidence , 2017, Nucleic Acids Res..

[41]  Lars G Fritsche,et al.  Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies , 2017, Nature Genetics.

[42]  J. Knight,et al.  Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice , 2017, Scientific Reports.

[43]  Hannes P. Eggertsson,et al.  Whole genome characterization of sequence diversity of 15,220 Icelanders , 2017, Scientific Data.

[44]  J. Fontcuberta,et al.  Platelet count and plateletcrit are associated with an increased risk of venous thrombosis in females. Results from the RETROVE study. , 2017, Thrombosis research.

[45]  Tanya M. Teslovich,et al.  Genetic and Pharmacologic Inactivation of ANGPTL3 and Cardiovascular Disease , 2017, The New England journal of medicine.

[46]  David A. Knowles,et al.  Inferring relevant cell types for complex traits using single-cell gene expression , 2017, bioRxiv.

[47]  A. Keech,et al.  Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease , 2017, The New England journal of medicine.

[48]  Jiao Jiao,et al.  Yes‐Associated Protein Inhibits Transcription of Myocardin and Attenuates Differentiation of Vascular Smooth Muscle Cell from Cardiovascular Progenitor Cell Lineage , 2017, Stem cells.

[49]  Evan Z. Macosko,et al.  Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types , 2017, Nature Genetics.

[50]  Gerard Tromp,et al.  Meta-Analysis of Genome-Wide Association Studies for Abdominal Aortic Aneurysm Identifies Four New Disease-Specific Risk Loci , 2017, Circulation research.

[51]  N. Roetker,et al.  Lifetime Risk and Risk Factors for Abdominal Aortic Aneurysm in a 24-Year Prospective Study: The ARIC Study (Atherosclerosis Risk in Communities) , 2016, Arteriosclerosis, thrombosis, and vascular biology.

[52]  Alan M. Kwong,et al.  Next-generation genotype imputation service and methods , 2016, Nature Genetics.

[53]  Shane A. McCarthy,et al.  Reference-based phasing using the Haplotype Reference Consortium panel , 2016, Nature Genetics.

[54]  M. Stuntz.  Modeling the Burden of Abdominal Aortic Aneurysm in the USA in 2013 , 2016, Cardiology.

[55]  Andrew D. Rouillard,et al.  Enrichr: a comprehensive gene set enrichment analysis web server 2016 update , 2016, Nucleic Acids Res..

[56]  D. Gudbjartsson,et al.  Variants with large effects on blood lipids and the role of cholesterol and triglycerides in coronary disease , 2016, Nature Genetics.

[57]  H. Burdett.  Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia , 2016, Annals of clinical biochemistry.

[58]  Mary Goldman,et al.  Exploring the phenotypic consequences of tissue specific gene expression variation inferred from GWAS summary statistics , 2016, Nature Communications.

[59]  F. Cunningham,et al.  The Ensembl Variant Effect Predictor , 2016, Genome Biology.

[60]  M. Schermerhorn,et al.  Abdominal aortic aneurysms in women. , 2016, Journal of vascular surgery.

[61]  A. Folsom,et al.  Circulating biomarkers and abdominal aortic aneurysm incidence: The Atherosclerosis Risk in Communities (ARIC) study , 2016 .

[62]  Gabor T. Marth,et al.  A global reference for human genetic variation , 2015, Nature.

[63]  J. Martínez-González,et al.  Expression and Cellular Localization of 15-Hydroxy-Prostaglandin-Dehydrogenase in Abdominal Aortic Aneurysm , 2015, PloS one.

[64]  C. Pilarsky,et al.  Differential gene expression in human abdominal aortic aneurysm and aortic occlusive disease , 2015, Oncotarget.

[65]  Bjarni V. Halldórsson,et al.  Large-scale whole-genome sequencing of the Icelandic population , 2015, Nature Genetics.

[66]  A. Regev,et al.  Spatial reconstruction of single-cell gene expression , 2015, Nature Biotechnology.

[67]  S. Thompson,et al.  Multivariable Mendelian Randomization: The Use of Pleiotropic Genetic Variants to Estimate Causal Effects , 2015, American journal of epidemiology.

[68]  J. Hirschhorn,et al.  Biological interpretation of genome-wide association studies using predicted gene functions , 2015, Nature Communications.

[69]  J. Mayne,et al.  Variable effects of gender and Western diet on lipid and glucose homeostasis in aged PCSK9‐deficient C57BL/6 mice 性别与西方饮食对CSK9基因缺陷的PC57BL/6老龄小鼠的脂质以及葡萄糖内稳态的不同影响 , 2015, Journal of diabetes.

[70]  W. Huber,et al.  Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 , 2014, Genome Biology.

[71]  P. Tsao,et al.  miR-24 limits aortic vascular inflammation and murine abdominal aneurysm development , 2014, Nature Communications.

[72]  M. Daly,et al.  LD Score regression distinguishes confounding from polygenicity in genome-wide association studies , 2014, Nature Genetics.

[73]  Melissa A. Basford,et al.  Systematic comparison of phenome-wide association study of electronic medical record data and genome-wide association study data , 2013, Nature Biotechnology.

[74]  Simon C. Potter,et al.  A Variant in LDLR Is Associated With Abdominal Aortic Aneurysm , 2013, Circulation. Cardiovascular genetics.

[75]  B. Nordestgaard,et al.  Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. , 2013, European heart journal.

[76]  C. Wallace,et al.  Bayesian Test for Colocalisation between Pairs of Genetic Association Studies Using Summary Statistics , 2013, PLoS genetics.

[77]  Wei Shi,et al.  featureCounts: an efficient general purpose program for assigning sequence reads to genomic features , 2013, Bioinform..

[78]  D. Harats,et al.  Apolipoprotein A-V modulates multiple atherogenic mechanisms in a mouse model of disturbed clearance of triglyceride-rich lipoproteins. , 2012, Atherosclerosis.

[79]  Y. E. Chen,et al.  Yap1 Protein Regulates Vascular Smooth Muscle Cell Phenotypic Switch by Interaction with Myocardin* , 2012, The Journal of Biological Chemistry.

[80]  P. Tsao,et al.  MicroRNA-21 Blocks Abdominal Aortic Aneurysm Development and Nicotine-Augmented Expansion , 2012, Science Translational Medicine.

[81]  P. Tsao,et al.  Transcriptional profiling and network analysis of the murine angiotensin II-induced abdominal aortic aneurysm. , 2011, Physiological genomics.

[82]  Ulrich Bodenhofer,et al.  APCluster: an R package for affinity propagation clustering , 2011, Bioinform..

[83]  Gary King,et al.  MatchIt: Nonparametric Preprocessing for Parametric Causal Inference , 2011 .

[84]  C. Twine,et al.  Systematic review and meta‐analysis of the effects of statin therapy on abdominal aortic aneurysms , 2011, The British journal of surgery.

[85]  P. Visscher,et al.  GCTA: a tool for genome-wide complex trait analysis. , 2011, American journal of human genetics.

[86]  Gerard Tromp,et al.  Genome-wide association study identifies a sequence variant within the DAB2IP gene conferring susceptibility to abdominal aortic aneurysm , 2010, Nature Genetics.

[87]  Yun Li,et al.  METAL: fast and efficient meta-analysis of genomewide association scans , 2010, Bioinform..

[88]  J. Marchini,et al.  Genotype imputation for genome-wide association studies , 2010, Nature Reviews Genetics.

[89]  B. Jacobsen,et al.  Risk Factors for Abdominal Aortic Aneurysms: A 7-Year Prospective Study: The Tromsø Study, 1994–2001 , 2009, Circulation.

[90]  Mathieu Bastian,et al.  Gephi: An Open Source Software for Exploring and Manipulating Networks , 2009, ICWSM.

[91]  Pall I. Olason,et al.  Detection of sharing by descent, long-range phasing and haplotype imputation , 2008, Nature Genetics.

[92]  B. Staels,et al.  Atheroprotective Effect of Human Apolipoprotein A5 in a Mouse Model of Mixed Dyslipidemia , 2008, Circulation research.

[93]  Jean-Loup Guillaume,et al.  Fast unfolding of communities in large networks , 2008, 0803.0476.

[94]  Manuel A. R. Ferreira,et al.  PLINK: a tool set for whole-genome association and population-based linkage analyses. , 2007, American journal of human genetics.

[95]  E. Hanssen,et al.  MAGP-2 Has Multiple Binding Regions on Fibrillins and Has Covalent Periodic Association with Fibrillin-containing Microfibrils* , 2004, Journal of Biological Chemistry.

[96]  D. Nyholt.  A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. , 2004, American journal of human genetics.

[97]  M. Mann,et al.  A Urokinase Receptor-associated Protein with Specific Collagen Binding Properties* , 2000, The Journal of Biological Chemistry.

[98]  A. Algra,et al.  Second Manifestations of ARTerial disease (SMART) study: Rationale and design , 1999, European Journal of Epidemiology.

[99]  A. Hofman,et al.  Aneurysms of the abdominal aorta in older adults. The Rotterdam Study. , 1995, American journal of epidemiology.

[100]  F. Macrae,et al.  Impact of a hospital‐based register on the management of familial adenomatous polyposis (for editorial comment, see page 546; see also page 557) , 1989, The Medical journal of Australia.

[101]  Ashraf Mansour Habib Mansour,et al.  The Society for Vascular Surgery practice guidelines on the care of patients with an abdominal aortic aneurysm , 2018, Journal of vascular surgery.

[102]  K. Hveem,et al.  COHORT PROFILE Cohort Profile : The HUNT Study , Norway , 2013 .

[103]  Simon C. Potter,et al.  Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1. , 2011, American journal of human genetics.