Genetic interactions with age, sex, body mass index, and hypertension in relation to atrial fibrillation: the AFGen consortium

Autor: David Conen, Bruce M. Psaty, Ingrid E. Christophersen, Olle Melander, Xiuqing Guo, Bruno H. Stricker, Martina Müller-Nurasyid, Gunnar Engström, Emelia J. Benjamin, Joshua C. Bis, Mina K. Chung, Jerome I. Rotter, Bastiaan Geelhoed, Susan R. Heckbert, Elsayed Z. Soliman, Marcus E. Kleber, Mika Kähönen, Alvaro Alonso, Sébastien Thériault, Henry J. Lin, Marcus Dörr, Kjell Nikus, Peter W. Macfarlane, Christine M. Albert, André G. Uitterlinden, Derek Klarin, Ian Ford, John Barnard, Andreas Martinsson, Lynda M. Rose, Lu-Chen Weng, Jie Yao, Nona Sotoodehnia, Tamara B. Harris, Bouwe P. Krijthe, Jan Heeringa, Moritz F. Sinner, Dan M. Roden, Leo-Pekka Lyytikäinen, Jonathan D. Smith, Stephan B. Felix, Uwe Völker, Albert V. Smith, J. Wouter Jukema, Alexander Teumer, David R. Van Wagoner, Patrick T. Ellinor, J. Gustav Smith, Winfried März, Vilmundur Gudnason, Steven A. Lubitz, Graciela E. Delgado, Daniel I. Chasman, Oscar H. Franco, Peter Weeke, M. Benjamin Shoemaker, Pedro L. Teixeira, Stella Trompet, Dan E. Arking, Melanie Waldenberger, Michiel Rienstra, Kent D. Taylor, Joshua C. Denny, Pim van der Harst, Terho Lehtimäki, Lenore J. Launer, Stefan Kääb, Kathryn L. Lunetta, Guillaume Paré, Niek Verweij
Přispěvatelé: Cardiovascular Centre (CVC), Læknadeild (HÍ), Faculty of Medicine (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Erasmus MC other, Epidemiology, Internal Medicine
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
0301 basic medicine
Aldurshópar
lcsh:Medicine
Physiology
Genome-wide association study
030204 cardiovascular system & hematology
VARIANTS
Cardiovascular
Bioinformatics
Genome-wide association studies
Body Mass Index
0302 clinical medicine
DESIGN
Risk Factors
Atrial Fibrillation
Odds Ratio
2.1 Biological and endogenous factors
Aetiology
lcsh:Science
FAMILIAL AGGREGATION
2. Zero hunger
Sex Characteristics
Multidisciplinary
Age Factors
Family aggregation
Atrial fibrillation
Single Nucleotide
Middle Aged
3. Good health
ENVIRONMENT INTERACTION
Háþrýstingur
Heart Disease
Pair 4
Hypertension
Líkamsþyngd
Medical genetics
HEART-FAILURE
Female
Chromosomes
Human
Pair 4
Human
medicine.medical_specialty
Cardiology
Locus (genetics)
Polymorphism
Single Nucleotide
Article
Chromosomes
03 medical and health sciences
Genetic
Genetics
medicine
Erfðafræði
Humans
Genetic Predisposition to Disease
Polymorphism
Allele
GENOME-WIDE ASSOCIATION
CHROMOSOME 4Q25
METAANALYSIS
Aged
business.industry
Prevention
lcsh:R
Human Genome
Reproducibility of Results
Epistasis
Genetic
Rannsóknir
medicine.disease
R1
030104 developmental biology
Genetic Loci
Genetic marker
LONE
Hjartasjúkdómar
Epistasis
RISK-FACTORS
lcsh:Q
business
Body mass index
Genome-Wide Association Study
Zdroj: Scientific Reports, 7:11303. Nature Publishing Group
Scientific reports, vol 7, iss 1
Scientific Reports, 7
Scientific Reports
Scientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
Sci. Rep. 7:11303 (2017)
ISSN: 2682-0110
2045-2322
Popis: It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10−5). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10−8). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.
This work is funded by the European Commision’s Horizon 2020 research and innovation programme (grant number 633196: CATCH ME to Dr. Sinner). AGES: The Age, Gene/Environment Susceptibility Reykjavik Study is funded by NIH contract N01-AG-12100. ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. This work was additionally supported by American Heart Association grant 16EIA26410001 (Alonso). BioVU: The dataset used in the analyses described were obtained from Vanderbilt University Medical Centers BioVU which is supported by institutional funding and by the Vanderbilt CTSA grant UL1 TR000445 from NCATS/NIH. Genome-wide genotyping was funded by NIH grants RC2GM092618 from NIGMS/OD and U01HG004603 from NHGRI/NIGMS. CCAF: R01 HL090620 and R01 HL111314 from the National Heart, Lung, and Blood Institute (Chung, Barnard, J. Smith, Van Wagoner); NIH/NCRR, CTSA 1UL-RR024989 (Chung, Van Wagoner); Heart and Vascular Institute, Department of Cardiovascular Medicine, Cleveland Clinic (Chung); Tomsich Atrial Fibrillation Research Fund (Chung); Leducq Foundation 07-CVD 03 (Van Wagoner, Chung); Atrial Fibrillation Innovation Center, State of Ohio (Van Wagoner, Chung). CHS: This Cardiovascular Health Study research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and R01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Psaty serves on the DSMB of a clinical trial funded by Zoll LifeCor and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. FINCAVAS: The Finnish Cardiovascular Study (FINCAVAS) has been financially supported by the Competitive Research Funding of the Tampere University Hospital (Grant 9M048 and 9N035), the Finnish Cultural Foundation, the Finnish Foundation for Cardiovascular Research, the Emil Aaltonen Foundation, Finland, and the Tampere Tuberculosis Foundation. FHS: Funding for SHARe Affymetrix genotyping was provided by NHLBI Contract N02-HL-64278. SHARe Illumina genotyping was provided under an agreement between Illumina and Boston University. Funding support for the FHS through 1R01HL128914; 2R01 HL092577; HHSN268201500001I; N01-HC 25195; and Framingham Atrial Fibrillation/Flutter reviewed through 2012 dataset was provided by NHLBI grants 1R01HL092577, 1R01HL102214, 1RC1HL101056 and NINDS grant 6R01-NS-17950. LURIC: The Ludwigshafen Risk and Cardiovascular Health study was supported by the seventh framework program of the European commission (RiskyCAD, grant agreement number 305739). Support for genotyping was provided by the seventh framework program of the European commission (AtheroRemo, grant agreement number 201668). MESA: The Multi-Ethnic Study of Atherosclerosis study was supported by NIH contracts HHSN2682015000031, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and by grants UL1-TR-000040, UL1-TR-001079, and UL1-RR-025005 from NCRR. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02-HL-6-4278. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. PREVEND: The PREVEND study is supported by the Dutch Kidney Foundation (grant E0.13) and the Netherlands Heart Foundation (grant NHS2010B280). Dr. M. Rienstra is supported by grants from the Netherlands Organization for Scientific Research (Veni grant 016.136.055). PROSPER: The PROSPER study was supported by an investigator initiated grant obtained from Bristol-Myers Squibb. Prof. Dr. J. W. Jukema is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping was provided by the seventh framework program of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). RS: The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam; the Netherlands Organization for Scientific Research; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly; The Netherlands Heart Foundation; the Ministry of Education, Culture and Science; the Ministry of Health Welfare and Sports; the European Commission; and the Municipality of Rotterdam. Support for genotyping was provided by the Netherlands Organization for Scientific Research (NWO) (175.010.2005.011, 911.03.012) and Research Institute for Diseases in the Elderly (RIDE). Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics, Inc., and AXA. Nestlé Nutrition (Nestec Ltd.), Metagenics, Inc., and AXA had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. SHIP: SHIP is part of the Community Medicine Research net of the University of Greifswald, Germany, which is funded by the Federal Ministry of Education and Research (grants no. 01ZZ9603, 01ZZ0103, and 01ZZ0403), the Ministry of Cultural Affairs as well as the Social Ministry of the Federal State of Mecklenburg-West Pomerania, and the network ‘Greifswald Approach to Individualized Medicine (GANI_MED)’ funded by the Federal Ministry of Education and Research (grant 03IS2061A). Genome-wide data have been supported by the Federal Ministry of Education and Research (grant no. 03ZIK012) and a joint grant from Siemens Healthcare, Erlangen, Germany and the Federal State of Mecklenburg- West Pomerania. The University of Greifswald is a member of the Caché Campus program of the InterSystems GmbH.
Databáze: OpenAIRE
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