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Novel genetic loci ...
Novel genetic loci associated with long-term deterioration in blood lipid concentrations and coronary artery disease in European adults
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- Varga, Tibor V. (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Kurbasic, Azra (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Aine, Mattias (author)
- Lund University,Lunds universitet,Avdelningen för molekylär hematologi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Hematology (DMH),Department of Laboratory Medicine,Faculty of Medicine,Skåne University Hospital
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- Eriksson, Pontus (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital
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- Ali, Ashfaq (author)
- Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit,Univ Cambridge, Epidemiol Unit, Med Res Council,Skåne University Hospital,University of Cambridge
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- Hindy, George (author)
- Skåne Univ Hosp, Diabet & Cardiovasc Dis Genet Epidemiol,Skåne University Hospital
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- Gustafsson, Stefan (author)
- Uppsala University,Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi
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- Luan, Jian'an (author)
- Univ Cambridge, Epidemiol Unit, Med Res Council,University of Cambridge
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- Shungin, Dmitry (author)
- Umeå University,Lund University,Lunds universitet,Umeå universitet,Institutionen för odontologi,Lund Univ, Skane Univ Hosp, Malmo, Sweden,Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Odontol;Umeå Univ, Dept Publ Hlth & Clin Med,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Chen, Yan (author)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Schulz, Christina Alexandra (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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- Nilsson, Peter M. (author)
- Lund University,Lunds universitet,Internmedicin - epidemiologi,Forskargrupper vid Lunds universitet,Internal Medicine - Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Hallmans, Göran, 1947- (author)
- Umeå University,Umeå universitet,Enheten för biobanksforskning,Umeå Univ, Dept Biobank Res
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- Barroso, Ines (author)
- Wellcome Trust Sanger Inst.;Addenbrookes Hosp, Metab Res Labs, Cambridge, Hosp, Metab Res Labs; Addenbrookes Hosp, NIHR Cambridge BiomeEngland.;Addenbrookes Hosp, NIHR Cambridge Biomed Res Ctr,Wellcome Trust Sanger Institute,Addenbrooke's Hospital
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- Deloukas, Panos (author)
- Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst.;King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah,Queen Mary University,King Abdulaziz University
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- Langenberg, Claudia (author)
- Univ Cambridge, Epidemiol Unit, Med Res Council,University of Cambridge
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- Scott, Robert A. (author)
- Univ Cambridge, Epidemiol Unit, Med Res Council
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- Wareham, Nicholas J. (author)
- Univ Cambridge, Epidemiol Unit, Med Res Council,University of Cambridge
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- Lind, Lars (author)
- Uppsala University,Uppsala universitet,Kardiovaskulär epidemiologi
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- Ingelsson, Erik, 1975- (author)
- Uppsala University,Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford,Wellcome Trust Centre for Human Genetics
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- Melander, Olle (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups,Skåne University Hospital
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- Orho-Melander, Marju (author)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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- Renström, Frida (author)
- Umeå University,Lund University,Lunds universitet,Umeå universitet,Enheten för biobanksforskning,Lund Univ, Skane Univ Hosp, Malmo, Sweden,Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Biobank Res,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital
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- Franks, Paul W. (author)
- Umeå University,Lund University,Lunds universitet,Umeå universitet,Medicin,Lund Univ, Skane Univ Hosp, Malmo, Sweden ; Harvard, Boston, MA USA,Lund Univ, Skåne Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit.;Umeå Univ, Dept Publ Hlth & Clin Med;Harvard TH Chan Sch Publ Hlth, Dept Nutr,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups,Skåne University Hospital,Harvard University
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(creator_code:org_t)
- 2016-11-17
- 2017
- English.
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In: International Journal of Epidemiology. - : Oxford University Press (OUP). - 0300-5771 .- 1464-3685. ; 46:4, s. 1211-1222
- Related links:
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http://dx.doi.org/10...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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Abstract
Subject headings
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- Background: Cross-sectional genome-wide association studies have identified hundreds of loci associated with blood lipids and related cardiovascular traits, but few genetic association studies have focused on long-term changes in blood lipids.Methods: Participants from the GLACIER Study (N-max = 3492) were genotyped with the MetaboChip array, from which 29 387 SNPs (single nucleotide polymorphisms;replication, fine-mapping regions and wildcard SNPs for lipid traits) were extracted for association tests with 10-year change in total cholesterol (Delta TC) and triglycerides (Delta TG). Four additional prospective cohort studies (MDC, PIVUS, ULSAM, MRC Ely; N-max = 8263 participants) were used for replication. We conducted an in silico look-up for association with coronary artery disease (CAD) in the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAMplusC4D) Consortium (N similar to 190 000) and functional annotation for the top ranking variants.Results: In total, 956 variants were associated (P < 0.01) with either Delta TC or Delta TG in GLACIER. In GLACIER, chr19:50121999 at APOE was associated with Delta TG and multiple SNPs in the APOA1/A4/C3/A5 region at genome-wide significance (P < 5 x 10(-8)), whereas variants in four loci, DOCK7, BRE, SYNE1 and KCNIP1, reached study-wide significance (P < 1.7 x 10(-6)). The rs7412 variant at APOE was associated with DTC in GLACIER (P < 1.7 x 10(-6)). In pooled analyses of all cohorts, 139 SNPs at six and five loci were associated with Delta TC and for Delta TG, respectively (P < 10(-3)). Of these, a variant at CAPN3 (P = 1.2 x 10(-4)), multiple variants at HPR (P-min = 1.5 x 10(-6)) and a variant at SIX5 (P = 1.9 x 10(-4)) showed evidence for association with CAD.Conclusions: We identified seven novel genomic regions associated with long-term changes in blood lipids, of which three also raise CAD risk.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Arbetsmedicin och miljömedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Occupational Health and Environmental Health (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- Prospective cohort study
- longitudinal analysis
- total cholesterol
- morbidity
- triglycerides
- single nucleotide polymorphism
- genetic epidemiology
- Genetic epidemiology
- Longitudinal analysis
- Morbidity
- Prospective cohort study
- Single nucleotide polymorphism
- Total cholesterol
- Triglycerides
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Varga, Tibor V.
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Kurbasic, Azra
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Aine, Mattias
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Eriksson, Pontus
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Ali, Ashfaq
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Hindy, George
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Gustafsson, Stef ...
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Luan, Jian'an
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Shungin, Dmitry
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Chen, Yan
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Schulz, Christin ...
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Nilsson, Peter M ...
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Hallmans, Göran, ...
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Barroso, Ines
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Deloukas, Panos
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Langenberg, Clau ...
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Scott, Robert A.
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Wareham, Nichola ...
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Lind, Lars
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Ingelsson, Erik, ...
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Melander, Olle
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Orho-Melander, M ...
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Renström, Frida
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Franks, Paul W.
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Uppsala University
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Umeå University
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Lund University