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Comprehensive Analy...
Comprehensive Analysis of Established Dyslipidemia-Associated Loci in the Diabetes Prevention Program
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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
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- Winters, Alexandra H. (author)
- University of Maryland
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- Jablonski, Kathleen A. (author)
- George Washington University
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- Horton, Edward S. (author)
- Joslin Diabetes Center,Harvard University
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- Khare-Ranade, Prajakta (author)
- Washington University in St. Louis
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- Knowler, William C. (author)
- National Institute of Diabetes and Digestive and Kidney Diseases
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- Marcovina, Santica M. (author)
- University of Washington
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- Renström, Frida (author)
- Umeå University,Lund University,Lunds universitet,Umeå universitet,Enheten för biobanksforskning,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Watson, Karol E. (author)
- University of California, Los Angeles
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- Goldberg, Ronald (author)
- University of Miami
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- Florez, José C. (author)
- Broad Institute,Massachusetts General Hospital,Harvard University
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- Pollin, Toni I. (author)
- University of Maryland
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- Franks, Paul W. (author)
- Umeå University,Lund University,Lunds universitet,Umeå universitet,Medicin,Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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(creator_code:org_t)
- Lippincott Williams & Wilkins, 2016
- 2016
- English.
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In: Circulation. - : Lippincott Williams & Wilkins. - 1942-325X .- 1942-3268. ; 9:6, s. 495-503
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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: We assessed whether 234 established dyslipidemia-associated loci modify the effects of metformin treatment and lifestyle intervention (versus placebo control) on lipid and lipid subfraction levels in the Diabetes Prevention Program randomized controlled trial. Methods and Results: We tested gene treatment interactions in relation to baseline-adjusted follow-up blood lipid concentrations (high-density lipoprotein [HDL] and low-density lipoprotein-cholesterol, total cholesterol, and triglycerides) and lipoprotein subfraction particle concentrations and size in 2993 participants with pre-diabetes. Of the previously reported single-nucleotide polymorphism associations, 32.5% replicated at P<0.05 with baseline lipid traits. Trait-specific genetic risk scores were robustly associated (3x10(-4)>P>1.1x10(-16)) with their respective baseline traits for all but 2 traits. Lifestyle modified the effect of the genetic risk score for large HDL particle numbers, such that each risk allele of the genetic risk scores was associated with lower concentrations of large HDL particles at follow-up in the lifestyle arm (beta=-0.11 mu mol/L per genetic risk scores risk allele; 95% confidence interval, -0.188 to -0.033; P=5x10(-3); P-interaction=1x10(-3) for lifestyle versus placebo), but not in the metformin or placebo arms (P>0.05). In the lifestyle arm, participants with high genetic risk had more favorable or similar trait levels at 1-year compared with participants at lower genetic risk at baseline for 17 of the 20 traits. Conclusions: Improvements in large HDL particle concentrations conferred by lifestyle may be diminished by genetic factors. Lifestyle intervention, however, was successful in offsetting unfavorable genetic loading for most lipid traits.
Subject headings
- 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)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- clinical trial
- genetics
- lifestyle
- lipids
- lipoproteins
- molecular epidemiology
- polymorphism
- genetic
- clinical trial
- genetics
- lifestyle
- lipids
- lipoproteins
- molecular epidemiology
- polymorphism, genetic
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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Winters, Alexand ...
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Jablonski, Kathl ...
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Horton, Edward S ...
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Khare-Ranade, Pr ...
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Knowler, William ...
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show more...
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Marcovina, Santi ...
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Renström, Frida
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Watson, Karol E.
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Goldberg, Ronald
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Florez, José C.
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Pollin, Toni I.
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Franks, Paul W.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cardiac and Card ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Circulation
- By the university
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Umeå University
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Lund University