Browsing by Author "Sattar, Naveed"

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    Genome-wide association study in 79,366 European-ancestry individuals informs the genetic architecture of 25-hydroxyvitamin D levels
    (Nature Publishing Group, 2018-01-17) Jiang, Xia; O’Reilly, Paul F.; Aschard, Hugues; Hsu, Yi-Hsiang; Richards, J. Brent; Dupuis, Josée; Ingelsson, Erik; Karasik, David; Pilz, Stefan; Berry, Diane; Kestenbaum, Bryan; Zheng, Jusheng; Luan, Jianan; Sofianopoulou, Eleni; Streeten, Elizabeth A.; Albanes, Demetrius; Lutsey, Pamela L.; Yao, Lu; Tang, Weihong; Econs, Michael J.; Wallaschofski, Henri; Völzke, Henry; Zhou, Ang; Power, Chris; McCarthy, Mark I.; Michos, Erin D.; Boerwinkle, Eric; Weinstein, Stephanie J.; Freedman, Neal D.; Huang, Wen-Yi; Van Schoor, Natasja M.; Velde, Nathalie van der; de Groot, Lisette C. P. G. M.; Enneman, Anke; Cupples, L. Adrienne; Booth, Sarah L.; Vasan, Ramachandran S.; Liu, Ching-Ti; Zhou, Yanhua; Ripatti, Samuli; Ohlsson, Claes; Vandenput, Liesbeth; Lorentzon, Mattias; Eriksson, Johan G.; Shea, M. Kyla; Houston, Denise K.; Kritchevsky, Stephen B.; Liu, Yongmei; Lohman, Kurt K.; Ferrucci, Luigi; Peacock, Munro; Gieger, Christian; Beekman, Marian; Slagboom, Eline; Deelen, Joris; Heemst, Diana van; Kleber, Marcus E.; März, Winfried; de Boer, Ian H.; Wood, Alexis C.; Rotter, Jerome I.; Rich, Stephen S.; Robinson-Cohen, Cassianne; Heijer, Martin den; Jarvelin, Marjo-Riitta; Cavadino, Alana; Joshi, Peter K.; Wilson, James F.; Hayward, Caroline; Lind, Lars; Michaëlsson, Karl; Trompet, Stella; Zillikens, M. Carola; Uitterlinden, Andre G.; Rivadeneira, Fernando; Broer, Linda; Zgaga, Lina; Campbell, Harry; Theodoratou, Evropi; Farrington, Susan M.; Timofeeva, Maria; Dunlop, Malcolm G.; Valdes, Ana M.; Tikkanen, Emmi; Lehtimäki, Terho; Lyytikäinen, Leo-Pekka; Kähönen, Mika; Raitakari, Olli T.; Mikkilä, Vera; Ikram, M. Arfan; Sattar, Naveed; Jukema, J. Wouter; Wareham, Nicholas J.; Langenberg, Claudia; Forouhi, Nita G.; Gundersen, Thomas E.; Khaw, Kay-Tee; Butterworth, Adam S.; Danesh, John; Spector, Timothy; Wang, Thomas J.; Hyppönen, Elina; Kraft, Peter; Kiel, Douglas P.; Medicine, School of Medicine
    Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand the previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P = 4.7×10-9 at rs8018720 in SEC23A, and P = 1.9×10-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels
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    Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
    (Springer Nature, 2019-01-07) Erzurumluoglu, A. Mesut; Liu, Mengzhen; Jackson, Victoria E.; Barnes, Daniel R.; Datta, Gargi; Melbourne, Carl A.; Young, Robin; Batini, Chiara; Surendran, Praveen; Jiang, Tao; Adnan, Sheikh Daud; Afaq, Saima; Agrawal, Arpana; Altmaier, Elisabeth; Antoniou, Antonis C.; Asselbergs, Folkert W.; Baumbach, Clemens; Bierut, Laura; Bertelsen, Sarah; Boehnke, Michael; Bots, Michiel L.; Brazel, David M.; Chambers, John C.; Chang-Claude, Jenny; Chen, Chu; Corley, Janie; Chou, Yi-Ling; David, Sean P.; Boer, Rudolf A. de; Leeuw, Christiaan A. de; Dennis, Joe G.; Dominiczak, Anna F.; Dunning, Alison M.; Easton, Douglas F.; Eaton, Charles; Elliott, Paul; Evangelou, Evangelos; Faul, Jessica D.; Foroud, Tatiana; Goate, Alison; Gong, Jian; Grabe, Hans J.; Haessler, Jeff; Haiman, Christopher; Hallmans, Göran; Hammerschlag, Anke R.; Harris, Sarah E.; Hattersley, Andrew; Heath, Andrew; Hsu, Chris; Iacono, William G.; Kanoni, Stavroula; Kapoor, Manav; Kaprio, Jaakko; Kardia, Sharon L.; Karpe, Fredrik; Kontto, Jukka; Kooner, Jaspal S.; Kooperberg, Charles; Kuulasmaa, Kari; Laakso, Markku; Lai, Dongbing; Langenberg, Claudia; Le, Nhung; Lettre, Guillaume; Loukola, Anu; Luan, Jian’an; Madden, Pamela A. F.; Mangino, Massimo; Marioni, Riccardo E.; Marouli, Eirini; Marten, Jonathan; Martin, Nicholas G.; McGue, Matt; Michailidou, Kyriaki; Mihailov, Evelin; Moayyeri, Alireza; Moitry, Marie; Müller-Nurasyid, Martina; Naheed, Aliya; Nauck, Matthias; Neville, Matthew J.; Nielsen, Sune Fallgaard; North, Kari; Perola, Markus; Pharoah, Paul D. P.; Pistis, Giorgio; Polderman, Tinca J.; Posthuma, Danielle; Poulter, Neil; Qaiser, Beenish; Rasheed, Asif; Reiner, Alex; Renström, Frida; Rice, John; Rohde, Rebecca; Rolandsson, Olov; Samani, Nilesh J.; Samuel, Maria; Schlessinger, David; Scholte, Steven H.; Scott, Robert A.; Sever, Peter; Shao, Yaming; Shrine, Nick; Smith, Jennifer A.; Starr, John M.; Stirrups, Kathleen; Stram, Danielle; Stringham, Heather M.; Tachmazidou, Ioanna; Tardif, Jean-Claude; Thompson, Deborah J.; Tindle, Hilary A.; Tragante, Vinicius; Trompet, Stella; Turcot, Valerie; Tyrrell, Jessica; Vaartjes, Ilonca; Leij, Andries R. van der; Meer, Peter van der; Varga, Tibor V.; Verweij, Niek; Völzke, Henry; Wareham, Nicholas J.; Warren, Helen R.; Weir, David R.; Weiss, Stefan; Wetherill, Leah; Yaghootkar, Hanieh; Yavas, Ersin; Jiang, Yu; Chen, Fang; Zhan, Xiaowei; Zhang, Weihua; Zhao, Wei; Zhao, Wei; Zhou, Kaixin; Amouyel, Philippe; Blankenberg, Stefan; Caulfield, Mark J.; Chowdhury, Rajiv; Cucca, Francesco; Deary, Ian J.; Deloukas, Panos; Angelantonio, Emanuele Di; Ferrario, Marco; Ferrières, Jean; Franks, Paul W.; Frayling, Tim M.; Frossard, Philippe; Hall, Ian P.; Hayward, Caroline; Jansson, Jan-Håkan; Jukema, J. Wouter; Kee, Frank; Männistö, Satu; Metspalu, Andres; Munroe, Patricia B.; Nordestgaard, Børge Grønne; Palmer, Colin N. A.; Salomaa, Veikko; Sattar, Naveed; Spector, Timothy; Strachan, David Peter; Harst, Pim van der; Zeggini, Eleftheria; Saleheen, Danish; Butterworth, Adam S.; Wain, Louise V.; Abecasis, Goncalo R.; Danesh, John; Tobin, Martin D.; Vrieze, Scott; Liu, Dajiang J.; Howson, Joanna M. M.; Medical and Molecular Genetics, School of Medicine
    Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10−8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10−8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10−3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.