Lu-Chen Weng1, Weihua Guan2, Lyn M Steffen1, James S Pankow1, Nathan Pankratz3, Ming-Huei Chen4, Mary Cushman5, Saonli Basu2, Aaron R Folsom1, Weihong Tang6. 1. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South Second Street, WBOB 300, Minneapolis, MN 55454, USA. 2. Division of Biostatistics, School of Public Health, University of Minnesota, 420 Delaware St SE, Minneapolis, MN 55455, USA. 3. Department of Laboratory Medicine and Pathology, School of Medicine, University of Minnesota, Mayo Mail Code 609, 420 Delaware Street S.E., Minneapolis, MN 55455, USA. 4. National Heart, Lung and Blood Institute's The Framingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung and Blood Institute, Framingham, MA, USA. 5. Departments of Medicine and Pathology, University of Vermont, Colchester Research Facility, 360 South Park Dr., Colchester, VT 05446, USA. 6. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, 1300 South Second Street, WBOB 300, Minneapolis, MN 55454, USA. Electronic address: tang0097@umn.edu.
Abstract
INTRODUCTION: Data from epidemiological studies and clinical trials suggest an influence of dietary and circulating polyunsaturated fatty acids (PUFAs) on the hemostasis profile. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) related to plasma PUFAs levels. We aimed to investigate whether the SNPs related to plasma PUFAs levels were also associated with plasma levels of hemostatic variables. MATERIALS AND METHODS: We tested the associations between 9 PUFA-related SNPs and 6 hemostatic variables in 9035 European Americans (EAs) and 2702 African Americans (AAs) in the Atherosclerosis Risk in Communities (ARIC) Study. We then conducted a replication study by looking-up our novel observed associations in three published GWAS for hemostatic factors in different EA populations. RESULTS: We observed a novel linoleic acid-related locus at the JMJD1C region associated with factor VII activity (FVIIc): rs10740118 and rs1935, Beta (p) = -1.31 (1 × 10-3) and 1.37 (5 × 10-4) in EAs, respectively, and - 1.24 (5 × 10-4) and 1.28 (3 × 10-4) in meta-analysis of EAs and AAs of ARIC. This novel association was replicated in two of three independent EA populations (p = 0.01 and 0.03 in meta-analyses). We confirmed previously reported associations at the docosapentaenoic acid-related GCKR locus with protein C and FVIIc and at JMJD1C with fibrinogen. Adjustment for plasma PUFAs did not abolish the associations between these loci and hemostatic variables. CONCLUSIONS: Our study identified a novel association for FVIIc at JMJD1C, a histone demethylase that plays a role in DNA repair and possibly transcription regulation and RNA processing.
INTRODUCTION: Data from epidemiological studies and clinical trials suggest an influence of dietary and circulating polyunsaturated fatty acids (PUFAs) on the hemostasis profile. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) related to plasma PUFAs levels. We aimed to investigate whether the SNPs related to plasma PUFAs levels were also associated with plasma levels of hemostatic variables. MATERIALS AND METHODS: We tested the associations between 9 PUFA-related SNPs and 6 hemostatic variables in 9035 European Americans (EAs) and 2702 African Americans (AAs) in the Atherosclerosis Risk in Communities (ARIC) Study. We then conducted a replication study by looking-up our novel observed associations in three published GWAS for hemostatic factors in different EA populations. RESULTS: We observed a novel linoleic acid-related locus at the JMJD1C region associated with factor VII activity (FVIIc): rs10740118 and rs1935, Beta (p) = -1.31 (1 × 10-3) and 1.37 (5 × 10-4) in EAs, respectively, and - 1.24 (5 × 10-4) and 1.28 (3 × 10-4) in meta-analysis of EAs and AAs of ARIC. This novel association was replicated in two of three independent EA populations (p = 0.01 and 0.03 in meta-analyses). We confirmed previously reported associations at the docosapentaenoic acid-related GCKR locus with protein C and FVIIc and at JMJD1C with fibrinogen. Adjustment for plasma PUFAs did not abolish the associations between these loci and hemostatic variables. CONCLUSIONS: Our study identified a novel association for FVIIc at JMJD1C, a histone demethylase that plays a role in DNA repair and possibly transcription regulation and RNA processing.
Authors: N A Zakai; L Lange; W T Longstreth; E S O'Meara; J L Kelley; M Fornage; D Nikerson; M Cushman; A P Reiner Journal: J Thromb Haemost Date: 2011-02 Impact factor: 5.824
Authors: Weihua Guan; Brian T Steffen; Rozenn N Lemaitre; Jason H Y Wu; Toshiko Tanaka; Ani Manichaikul; Millennia Foy; Luigi Ferrucci; Myriam Fornage; Dariush Mozafarrian; Michael Y Tsai; Lyn M Steffen; Stephen S Rich; Lu Wang; Jennifer A Nettleton; Weihong Tang; Xiangjun Gu; Stafania Bandinelli; Irena B King; Barbara McKnight; Bruce M Psaty; David Siscovick; Luc Djousse; Yii-Der Ida Chen Journal: Circ Cardiovasc Genet Date: 2014-05-13
Authors: Nicholas L Smith; Ming-Huei Chen; Abbas Dehghan; David P Strachan; Saonli Basu; Nicole Soranzo; Caroline Hayward; Igor Rudan; Maria Sabater-Lleal; Joshua C Bis; Moniek P M de Maat; Ann Rumley; Xiaoxiao Kong; Qiong Yang; Frances M K Williams; Veronique Vitart; Harry Campbell; Anders Mälarstig; Kerri L Wiggins; Cornelia M Van Duijn; Wendy L McArdle; James S Pankow; Andrew D Johnson; Angela Silveira; Barbara McKnight; Andre G Uitterlinden; Nena Aleksic; James B Meigs; Annette Peters; Wolfgang Koenig; Mary Cushman; Sekar Kathiresan; Jerome I Rotter; Edwin G Bovill; Albert Hofman; Eric Boerwinkle; Geoffrey H Tofler; John F Peden; Bruce M Psaty; Frank Leebeek; Aaron R Folsom; Martin G Larson; Timothy D Spector; Alan F Wright; James F Wilson; Anders Hamsten; Thomas Lumley; Jacqueline C M Witteman; Weihong Tang; Christopher J O'Donnell Journal: Circulation Date: 2010-03-15 Impact factor: 29.690
Authors: Andrea D Coviello; Robin Haring; Melissa Wellons; Dhananjay Vaidya; Terho Lehtimäki; Sarah Keildson; Kathryn L Lunetta; Chunyan He; Myriam Fornage; Vasiliki Lagou; Massimo Mangino; N Charlotte Onland-Moret; Brian Chen; Joel Eriksson; Melissa Garcia; Yong Mei Liu; Annemarie Koster; Kurt Lohman; Leo-Pekka Lyytikäinen; Ann-Kristin Petersen; Jennifer Prescott; Lisette Stolk; Liesbeth Vandenput; Andrew R Wood; Wei Vivian Zhuang; Aimo Ruokonen; Anna-Liisa Hartikainen; Anneli Pouta; Stefania Bandinelli; Reiner Biffar; Georg Brabant; David G Cox; Yuhui Chen; Steven Cummings; Luigi Ferrucci; Marc J Gunter; Susan E Hankinson; Hannu Martikainen; Albert Hofman; Georg Homuth; Thomas Illig; John-Olov Jansson; Andrew D Johnson; David Karasik; Magnus Karlsson; Johannes Kettunen; Douglas P Kiel; Peter Kraft; Jingmin Liu; Östen Ljunggren; Mattias Lorentzon; Marcello Maggio; Marcello R P Markus; Dan Mellström; Iva Miljkovic; Daniel Mirel; Sarah Nelson; Laure Morin Papunen; Petra H M Peeters; Inga Prokopenko; Leslie Raffel; Martin Reincke; Alex P Reiner; Kathryn Rexrode; Fernando Rivadeneira; Stephen M Schwartz; David Siscovick; Nicole Soranzo; Doris Stöckl; Shelley Tworoger; André G Uitterlinden; Carla H van Gils; Ramachandran S Vasan; H-Erich Wichmann; Guangju Zhai; Shalender Bhasin; Martin Bidlingmaier; Stephen J Chanock; Immaculata De Vivo; Tamara B Harris; David J Hunter; Mika Kähönen; Simin Liu; Pamela Ouyang; Tim D Spector; Yvonne T van der Schouw; Jorma Viikari; Henri Wallaschofski; Mark I McCarthy; Timothy M Frayling; Anna Murray; Steve Franks; Marjo-Riitta Järvelin; Frank H de Jong; Olli Raitakari; Alexander Teumer; Claes Ohlsson; Joanne M Murabito; John R B Perry Journal: PLoS Genet Date: 2012-07-19 Impact factor: 5.917