%0 Journal Article %J Nat Genet %D 2015 %T A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. %A Nikpay, Majid %A Goel, Anuj %A Won, Hong-Hee %A Hall, Leanne M %A Willenborg, Christina %A Kanoni, Stavroula %A Saleheen, Danish %A Kyriakou, Theodosios %A Nelson, Christopher P %A Hopewell, Jemma C %A Webb, Thomas R %A Zeng, Lingyao %A Dehghan, Abbas %A Alver, Maris %A Armasu, Sebastian M %A Auro, Kirsi %A Bjonnes, Andrew %A Chasman, Daniel I %A Chen, Shufeng %A Ford, Ian %A Franceschini, Nora %A Gieger, Christian %A Grace, Christopher %A Gustafsson, Stefan %A Huang, Jie %A Hwang, Shih-Jen %A Kim, Yun Kyoung %A Kleber, Marcus E %A Lau, King Wai %A Lu, Xiangfeng %A Lu, Yingchang %A Lyytikäinen, Leo-Pekka %A Mihailov, Evelin %A Morrison, Alanna C %A Pervjakova, Natalia %A Qu, Liming %A Rose, Lynda M %A Salfati, Elias %A Saxena, Richa %A Scholz, Markus %A Smith, Albert V %A Tikkanen, Emmi %A Uitterlinden, Andre %A Yang, Xueli %A Zhang, Weihua %A Zhao, Wei %A de Andrade, Mariza %A de Vries, Paul S %A Van Zuydam, Natalie R %A Anand, Sonia S %A Bertram, Lars %A Beutner, Frank %A Dedoussis, George %A Frossard, Philippe %A Gauguier, Dominique %A Goodall, Alison H %A Gottesman, Omri %A Haber, Marc %A Han, Bok-Ghee %A Huang, Jianfeng %A Jalilzadeh, Shapour %A Kessler, Thorsten %A König, Inke R %A Lannfelt, Lars %A Lieb, Wolfgang %A Lind, Lars %A Lindgren, Cecilia M %A Lokki, Marja-Liisa %A Magnusson, Patrik K %A Mallick, Nadeem H %A Mehra, Narinder %A Meitinger, Thomas %A Memon, Fazal-Ur-Rehman %A Morris, Andrew P %A Nieminen, Markku S %A Pedersen, Nancy L %A Peters, Annette %A Rallidis, Loukianos S %A Rasheed, Asif %A Samuel, Maria %A Shah, Svati H %A Sinisalo, Juha %A Stirrups, Kathleen E %A Trompet, Stella %A Wang, Laiyuan %A Zaman, Khan S %A Ardissino, Diego %A Eric Boerwinkle %A Borecki, Ingrid B %A Bottinger, Erwin P %A Buring, Julie E %A Chambers, John C %A Collins, Rory %A Cupples, L Adrienne %A Danesh, John %A Demuth, Ilja %A Elosua, Roberto %A Epstein, Stephen E %A Esko, Tõnu %A Feitosa, Mary F %A Franco, Oscar H %A Franzosi, Maria Grazia %A Granger, Christopher B %A Gu, Dongfeng %A Gudnason, Vilmundur %A Hall, Alistair S %A Hamsten, Anders %A Harris, Tamara B %A Hazen, Stanley L %A Hengstenberg, Christian %A Hofman, Albert %A Ingelsson, Erik %A Iribarren, Carlos %A Jukema, J Wouter %A Karhunen, Pekka J %A Kim, Bong-Jo %A Kooner, Jaspal S %A Kullo, Iftikhar J %A Lehtimäki, Terho %A Loos, Ruth J F %A Melander, Olle %A Metspalu, Andres %A Marz, Winfried %A Palmer, Colin N %A Perola, Markus %A Quertermous, Thomas %A Rader, Daniel J %A Ridker, Paul M %A Ripatti, Samuli %A Roberts, Robert %A Salomaa, Veikko %A Sanghera, Dharambir K %A Schwartz, Stephen M %A Seedorf, Udo %A Stewart, Alexandre F %A Stott, David J %A Thiery, Joachim %A Zalloua, Pierre A %A O'Donnell, Christopher J %A Reilly, Muredach P %A Assimes, Themistocles L %A Thompson, John R %A Erdmann, Jeanette %A Clarke, Robert %A Watkins, Hugh %A Kathiresan, Sekar %A McPherson, Ruth %A Deloukas, Panos %A Schunkert, Heribert %A Samani, Nilesh J %A Farrall, Martin %K Coronary Artery Disease %K Genome, Human %K Genome-Wide Association Study %K Humans %K Phenotype %X

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of ∼185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.

%B Nat Genet %V 47 %P 1121-1130 %8 2015 Oct %G eng %N 10 %1 https://www.ncbi.nlm.nih.gov/pubmed/26343387?dopt=Abstract %R 10.1038/ng.3396 %0 Journal Article %J PLoS One %D 2014 %T No evidence for genome-wide interactions on plasma fibrinogen by smoking, alcohol consumption and body mass index: results from meta-analyses of 80,607 subjects. %A Baumert, Jens %A Huang, Jie %A McKnight, Barbara %A Sabater-Lleal, Maria %A Steri, Maristella %A Chu, Audrey Y %A Trompet, Stella %A Lopez, Lorna M %A Fornage, Myriam %A Teumer, Alexander %A Tang, Weihong %A Rudnicka, Alicja R %A Mälarstig, Anders %A Hottenga, Jouke-Jan %A Kavousi, Maryam %A Lahti, Jari %A Tanaka, Toshiko %A Hayward, Caroline %A Huffman, Jennifer E %A Morange, Pierre-Emmanuel %A Rose, Lynda M %A Basu, Saonli %A Rumley, Ann %A Stott, David J %A Buckley, Brendan M %A de Craen, Anton J M %A Sanna, Serena %A Masala, Marco %A Biffar, Reiner %A Homuth, Georg %A Silveira, Angela %A Sennblad, Bengt %A Goel, Anuj %A Watkins, Hugh %A Müller-Nurasyid, Martina %A Rückerl, Regina %A Taylor, Kent %A Chen, Ming-Huei %A de Geus, Eco J C %A Hofman, Albert %A Witteman, Jacqueline C M %A de Maat, Moniek P M %A Palotie, Aarno %A Davies, Gail %A Siscovick, David S %A Kolcic, Ivana %A Wild, Sarah H %A Song, Jaejoon %A McArdle, Wendy L %A Ford, Ian %A Sattar, Naveed %A Schlessinger, David %A Grotevendt, Anne %A Franzosi, Maria Grazia %A Illig, Thomas %A Waldenberger, Melanie %A Lumley, Thomas %A Tofler, Geoffrey H %A Willemsen, Gonneke %A Uitterlinden, André G %A Rivadeneira, Fernando %A Räikkönen, Katri %A Chasman, Daniel I %A Folsom, Aaron R %A Lowe, Gordon D %A Westendorp, Rudi G J %A Slagboom, P Eline %A Cucca, Francesco %A Wallaschofski, Henri %A Strawbridge, Rona J %A Seedorf, Udo %A Koenig, Wolfgang %A Bis, Joshua C %A Mukamal, Kenneth J %A van Dongen, Jenny %A Widen, Elisabeth %A Franco, Oscar H %A Starr, John M %A Liu, Kiang %A Ferrucci, Luigi %A Polasek, Ozren %A Wilson, James F %A Oudot-Mellakh, Tiphaine %A Campbell, Harry %A Navarro, Pau %A Bandinelli, Stefania %A Eriksson, Johan %A Boomsma, Dorret I %A Dehghan, Abbas %A Clarke, Robert %A Hamsten, Anders %A Eric Boerwinkle %A Jukema, J Wouter %A Naitza, Silvia %A Ridker, Paul M %A Völzke, Henry %A Deary, Ian J %A Reiner, Alexander P %A Trégouët, David-Alexandre %A O'Donnell, Christopher J %A Strachan, David P %A Peters, Annette %A Smith, Nicholas L %K Alcohol Drinking %K Body Mass Index %K Fibrinogen %K Gene-Environment Interaction %K Genomics %K Humans %K Smoking %X

Plasma fibrinogen is an acute phase protein playing an important role in the blood coagulation cascade having strong associations with smoking, alcohol consumption and body mass index (BMI). Genome-wide association studies (GWAS) have identified a variety of gene regions associated with elevated plasma fibrinogen concentrations. However, little is yet known about how associations between environmental factors and fibrinogen might be modified by genetic variation. Therefore, we conducted large-scale meta-analyses of genome-wide interaction studies to identify possible interactions of genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentration. The present study included 80,607 subjects of European ancestry from 22 studies. Genome-wide interaction analyses were performed separately in each study for about 2.6 million single nucleotide polymorphisms (SNPs) across the 22 autosomal chromosomes. For each SNP and risk factor, we performed a linear regression under an additive genetic model including an interaction term between SNP and risk factor. Interaction estimates were meta-analysed using a fixed-effects model. No genome-wide significant interaction with smoking status, alcohol consumption or BMI was observed in the meta-analyses. The most suggestive interaction was found for smoking and rs10519203, located in the LOC123688 region on chromosome 15, with a p value of 6.2 × 10(-8). This large genome-wide interaction study including 80,607 participants found no strong evidence of interaction between genetic variants and smoking status, alcohol consumption or BMI on fibrinogen concentrations. Further studies are needed to yield deeper insight in the interplay between environmental factors and gene variants on the regulation of fibrinogen concentrations.

%B PLoS One %V 9 %P e111156 %8 2014 %G eng %N 12 %1 https://www.ncbi.nlm.nih.gov/pubmed/25551457?dopt=Abstract %R 10.1371/journal.pone.0111156