NDLI: Gene-Age Interactions in Blood Pressure Regulation: A Large-Scale Investigation with the CHARGE, Global BPgen, and ICBP Consortia

Content Provider	PubMed Central
Author	Simino, Jeannette Shi, Gang Bis, Joshua C. Chasman, Daniel I. Ehret, Georg B. Gu, Xiangjun Guo, Xiuqing Hwang, Shih-jen Sijbrands, Eric Smith, Albert V. Verwoert, Germaine C. Bragg-gresham, Jennifer L. Cadby, Gemma Chen, Peng Cheng, Ching-yu Corre, Tanguy Boer, Rudolf A. De Goel, Anuj Johnson, Toby Khor, Chiea-chuen Alizadeh, Behrooz Z. Boezen, H. Marike Bruinenberg, Marcel Franke, Lude Harst, Pim Van Der Hillege, Hans L. Van, Der Klauw Melanie M. Navis, Gerjan Ormel, Johan Postma, Dirkje S. Rosmalen, Judith G. M. Slaets, Joris P. Harold, Snieder Stolk, Ronald P. Wolffenbuttel, Bruce H. R. Wijmenga, Cisca Lluís-ganella, Carla Luan, Jian’an Lyytikäinen, Leo-pekka Nolte, Ilja M. Sim, Xueling Sõber, Siim Most, Peter J. Van Der Verweij, Niek Zhao, Jing Hua Amin, Najaf Boerwinkle, Eric Bouchard, Claude Dehghan, Abbas Eiriksdottir, Gudny Elosua, Roberto Franco, Oscar H. Gieger, Christian Harris, Tamara B. Serge, Hercberg Hofman, Albert James, Alan L. Johnson, Andrew D. Mika, Kähönen Khaw, Kay-tee Kutalik, Zoltan Larson, Martin G. Launer, Lenore J. Li, Guo Liu, Jianjun Liu, Kiang Morrison, Alanna C. Ong, Rick Twee-hee Papanicolau, George J. Penninx, Brenda W. Psaty, Bruce M. Raffel, Leslie J. Raitakari, Olli T. Rice, Kenneth Rivadeneira, Fernando Rose, Lynda M. Sanna, Serena Scott, Robert A. Siscovick, David S. Uitterlinden, Andre G. Vaidya, Dhananjay Vasan, Ramachandran S. Vithana, Eranga Nishanthie Völker, Uwe Henry, Völzke Watkins, Hugh Young, Terri L. Aung, Tin Bochud, Murielle Farrall, Martin Hartman, Catharina A. Laan, Maris Lakatta, Edward G. Lehtimäki, Terho Loos, Ruth J. F. Lucas, Gavin Pierre, Meneton Palmer, Lyle J. Rettig, Rainer Tai, E. Shyong Teo, Yik-ying Wareham, Nicholas J. Wong, Tien Yin Fornage, Myriam Gudnason, Vilmundur Levy, Daniel Palmas, Walter Ridker, Paul M. Rotter, Jerome I. Duijn, Cornelia M. Van Witteman, Jacqueline C. M. Chakravarti, Aravinda Rao, Dabeeru C.
Copyright Year	2014
Abstract	Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p ≤ 5 × 10−8) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 × 10−4) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations.
Related Links	http://dx.doi.org/10.1016/j.ajhg.2014.05.010
Ending Page	38
Page Count	15
Starting Page	24
File Format	PDF
ISSN	00029297
e-ISSN	15376605
Journal	American Journal of Human Genetics
Issue Number	1
Volume Number	95
Language	English
Publisher	Elsevier
Publisher Date	2014-07-01
Access Restriction	Open
Rights Holder	Elsevier
Subject Keyword	Genetics(clinical) Genetics Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Genetics Genetics (clinical)

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

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