A genome-wide association meta-analysis on lipoprotein (a) concentrations adjusted for apolipoprotein (a) isoforms
Year: 2017
Type: review
Study design: Observational Study
Abstract: High lipoprotein (a) [Lp(a)] concentrations are an independent risk factor for cardiovascular outcomes. Concentrations are strongly influenced by apo(a) kringle IV repeat isoforms. We aimed to identify genetic loci associated with Lp(a) concentrations using data from five genome-wide association studies (n = 13,781). We identified 48 independent SNPs in the LPA and 1 SNP in the APOE gene region to be significantly associated with Lp(a) concentrations. We also adjusted for apo(a) isoforms to identify loci affecting Lp(a) levels independently from them, which resulted in 31 SNPs (30 in the LPA , 1 in the APOE gene region). Seven SNPs showed a genome-wide significant association with coronary artery disease (CAD) risk. A rare SNP (rs186696265; MAF ∼1%) showed the highest effect on Lp(a) and was also associated with increased risk of CAD (odds ratio=1.73, P = 3.35 × 10 −30 ). Median Lp(a) values increased from 2.1 to 91.1 mg/dl with increasing number of Lp(a)-increasing alleles. We found the APOE2 -determining allele of rs7412 to be significantly associated with Lp(a) concentrations ( P = 3.47 × 10 −10 ). Each APOE2 allele decreased Lp(a) by 3.34 mg/dl corresponding to ∼15% of the populationʼns mean values. Performing a gene-based test of association, including suspected Lp(a) receptors and regulators, resulted in one significant association of the TLR2 gene with Lp(a) ( P = 3.4 × 10 −4 ). In summary, we identified a large number of independent SNPs in the LPA gene region, as well as the APOE2 allele, to be significantly associated with Lp(a) concentrations.
Source: Journal of Lipid Research
DOI: 10.1194/jlr.m076232
Authors: Salome Mack, Stefan Coassin, Rico Rueedi, Noha A. Yousri, Ilkka Seppälä, Christian Gieger, Sebastian Schönherr, Lukas Forer, Gertraud Erhart, Pedro Marques-Vidal, Janina S. Ried, Gerard Waeber, Sven Bergmann, Doreen Dähnhardt, Andrea Stöckl, Olli T. Raitakari, Mika Kähönen, Annette Peters, Thomas Meitinger, Konstantin Strauch, Ludmilla Kedenko, Bernhard Paulweber, Terho Lehtimäki, Steven C. Hunt, Peter Vollenweider, Claudia Lamina, Florian Kronenberg
Institutions: Innsbruck Medical University, Universität Innsbruck, SIB Swiss Institute of Bioinformatics, University of Lausanne, Weill Cornell Medical College in Qatar, Alexandria University, Tampere University, Fimlab (Finland), University of Tampere, Helmholtz Munich, Centre Hospitalier Universitaire Vaudois, University of Turku, Turku University Hospital, Tampere University Hospital, German Centre for Cardiovascular Research, German Center for Diabetes Research, Munich Cluster for Systems Neurology, Institut für Humangenetik, Technical University of Munich, Ludwig-Maximilians-Universität München, Paracelsus Medical University, University of Utah, Weill Cornell Medicine
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,706
Funders: National Science Foundation, GlaxoSmithKline, Qatar Foundation, Yrjö Jahnssonin Säätiö, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Kela, Academy of Finland, Bundesministerium für Bildung und Forschung, Austrian Science Fund, Suomen Kulttuurirahasto, Juho Vainion Säätiö, Emil Aaltosen Säätiö, Tampereen Tuberkuloosisäätiö, Paavo Nurmen Säätiö, Chinese Society of Clinical Oncology, Turun Yliopistollinen Keskussairaala, National Institutes of Health, Weill Cornell Medical College, Weill Cornell Medicine - Qatar, Helmholtz Zentrum München, National Heart, Lung, and Blood Institute
Awards: Foot movement representation in the human brain and its plasticity in spinal cord injured patients: Investigating the clinical application of the acquired data in neurological rehabilitation, Precision Polymerization, G1371966383, GENCAC - Minnesota Field Center, Monuments d'Art et d'Histoire, Fribourg District du Lac I, G1601895641, G1891033315, Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study, G2026946236, G2230772921, Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study, GENCAC - MOLECULAR GENETICS LABORATORY, G2939612130, G2957143966, G3111916513, G3248287424, G3302495997, GENCAC - Utah Field Center, G3758374299, G3858258543, Genetics of Coronary and Aortic Calcification (GENCAC), G4139205196, GENCAC - Birmingham Field Center, G4351223834, Aufstieg und Fall der Pasirah, A genome-wide approach to evaluate the genetic basis of lipoprotein(a), G4655867613, G4706061674, G5017959396, G5208171454, G5599442719, G5694967924, GENCAC - Framingham Field Center, G5770909501, GENCAC - North Carolina Field Center, G5949740445, G6355767702, G6802942620, G6927407676, Philosophical Methodology and Intuitions, GENCAC-Data Coordinating Center, G7262634952, Cardiovascular diseases and psychiatric disorders in the general population: a prospective follow-up study, G7540798381, GENCAC - Arterial Calcium Reading Center, G7975901996, Soins aux personnes âgées démentes en institution: analyse de l'influence des représentations des soignants sur leurs pratiques du toucher., G8253295407, GENCAC - CENTRAL BIOCHEMISTRY LABORATORY, G8499801373, G8694448641, G8775779249, ENTS: Entangled spin pairs in graphene
OpenAlex ID: W2616325230