期刊
JOURNAL OF MEDICAL GENETICS
卷 53, 期 7, 页码 441-449出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jmedgenet-2015-103439
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资金
- NIH [N01-AG-1-2100, HHSN271201200022C]
- NIA Intramural Research Program
- Hjartavernd (the Icelandic Heart Association)
- Althingi (the Icelandic Parliament)
- Home Office [780-TETRA]
- National Institute for Health Research (NIHR) Imperial College Healthcare NHS Trust (ICHNT)
- Imperial College Biomedical Research Centre (BRC)
- ICHNT
- Imperial College BRC
- MRC-PHE Centre for Environment and Health
- NIHR Health Protection Research Unit on Health Impact of Environmental Hazards
- National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C]
- NHLBI [HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393]
- National Institute on Aging (NIA) [R01AG023629]
- National Center for Advancing Translational Sciences
- CTSI grant [UL1TR000124]
- National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491]
- Medical Research Council UK
- Croatian Ministry of Science, Education and Sports [216-1080315-0302]
- European Union [LSHG-CT-2006-018947, 259679, 279143]
- Croatian Science Foundation [8875]
- European Commission FP6 STRP grant [018947 (LSHG-CT-2006-01947)]
- European Community [HEALTH-F4-2007-201413]
- European Commission under the programme Quality of Life and Management of the Living Resources of 5th Framework Programme [QLG2-CT-2002-01254]
- ENGAGE consortium
- CMSB
- Netherlands Organisation for Scientific Research [NWO-RFBR 047.017.043]
- Russian Foundation for Basic Research [NWO-RFBR 047.017.043]
- ZonMw grant [91111025]
- National Heart, Lung, and Blood Institute [R01-HL-087700, R01-HL-088215, R01-HL-117078]
- Chief Scientist Office of the Scottish Government Health Directorate [CZD/16/6]
- Scottish Funding Council [HR03006]
- UK's Medical Research Council
- Netherlands Organization of Scientific Research NWO [175.010.2007.006]
- Economic Structure Enhancing Fund (FES) of the Dutch government
- Ministry of Economic Affairs
- Ministry of Education, Culture and Science
- Ministry for Health, Welfare and Sports
- Northern Netherlands Collaboration of Provinces (SNN)
- Province of Groningen
- University Medical Center Groningen
- University of Groningen
- Dutch Kidney Foundation
- Dutch Diabetes Research Foundation
- Innovation-Oriented Research Program on Genomics (SenterNovem) [IGE05007]
- Centre for Medical Systems Biology
- Netherlands Consortium for Healthy Ageing [050-060-810]
- UnileverColworth
- BBMRI-NL, a Research Infrastructure - Dutch government [NWO 184.021.007]
- National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre Imperial College Healthcare NHS Trust
- British Heart Foundation [SP/04/002]
- Medical Research Council [G0601966, G0700931]
- Wellcome Trust [084723/Z/08/Z]
- NIHR [RP-PG-0407-10371]
- Action on Hearing Loss [G51]
- Division and the Board of Directors of the Leiden University Medical Center
- Leiden University, Research Profile Area 'Vascular and Regenerative Medicine'
- Dutch Science Organization (ZonMW-VENI Grant) [916.14.023]
- Chief Scientist Office of the Scottish Government
- Royal Society
- MRC Human Genetics Unit
- Arthritis Research UK
- Bristol-Myers Squibb
- Netherlands Heart Foundation [2001 D 032]
- European commission [223004]
- Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging) [050-060-810]
- Netherlands Organisation of Scientific Research NWO [175.010.2005.011, 911-03-012]
- Research Institute for Diseases in the Elderly [014-93-015, RIDE2]
- Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]
- Erasmus Medical Center
- Erasmus University, Rotterdam
- Netherlands Organization for the Health Research and Development (ZonMw)
- Research Institute for Diseases in the Elderly (RIDE)
- European Commission (DG XII)
- Municipality of Rotterdam
- University Medical Center, Netherlands
- Erasmus University Medical Center Rotterdam, Netherlands
- University of Utrecht, Netherlands
- Radboud Medical Center Nijmegen, Netherlands
- Parnassia Bavo group, Netherlands
- University of Groningen, Netherlands
- Netherlands Organization for Scientific Research NWO (Medical Research Council program) [GB-MW 940-38-011]
- Netherlands Organization for Scientific Research NWO (ZonMW Brainpower grant) [100-001-004]
- ZonMw Risk Behavior and Dependence grants [60-60600-97-118]
- ZonMw Culture and Health grant [261-98-710]
- Social Sciences Council [GB-MaGW 480-01-006, GB-MaGW 480-07-001, GB-MaGW 452-04-314, GB-MaGW 452-06-004]
- NWO large-sized investment grant [175.010.2003.005]
- NWO Longitudinal Survey and Panel Funding [481-08-013, 481-11-001]
- Dutch Ministry of Justice (WODC)
- European Science Foundation [FP-006]
- Biobanking and Biomolecular Resources Research Infrastructure BBMRI-NL [CP 32]
- MRC [G0601966, G0700931, MR/L01341X/1, MR/K002414/1, MC_PC_U127561128] Funding Source: UKRI
- Chief Scientist Office [CZD/16/6/4] Funding Source: researchfish
- Medical Research Council [MC_PC_U127561128, 1201677, G0601966, MR/L01341X/1, G0700931] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0611-10136] Funding Source: researchfish
Background So far, more than 170 loci have been associated with circulating lipid levels through genome-wide association studies (GWAS). These associations are largely driven by common variants, their function is often not known, and many are likely to be markers for the causal variants. In this study we aimed to identify more new rare and low-frequency functional variants associated with circulating lipid levels. Methods We used the 1000 Genomes Project as a reference panel for the imputations of GWAS data from similar to 60 000 individuals in the discovery stage and similar to 90 000 samples in the replication stage. Results Our study resulted in the identification of five new associations with circulating lipid levels at four loci. All four loci are within genes that can be linked biologically to lipid metabolism. One of the variants, rs116843064, is a damaging missense variant within the ANGPTL4 gene. Conclusions This study illustrates that GWAS with high-scale imputation may still help us unravel the biological mechanism behind circulating lipid levels.
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