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Identification of a...
Identification of a novel proinsulin-associated SNP and demonstration that proinsulin is unlikely to be a causal factor in subclinical vascular remodelling using Mendelian randomisation
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- Strawbridge, Rona J. (author)
- Karolinska Institutet
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- Silveira, Angela (author)
- Karolinska Institutet
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- den Hoed, Marcel (author)
- Uppsala universitet,Medicinsk genetik och genomik,Science for Life Laboratory, SciLifeLab
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show more...
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- Gustafsson, Stefan (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär epidemiologi
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- Luan, Jian'an (author)
- Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.
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- Rybin, Denis (author)
- Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA.
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- Dupuis, Josee (author)
- Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.;Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
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- Li-Gao, Ruifang (author)
- Leiden Univ, Dept Clin Epidemiol, Med Ctr, Leiden, Netherlands.
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- Kavousi, Maryam (author)
- Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
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- Dehghan, Abbas (author)
- Univ Med Ctr Rotterdam, Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England.
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- Haljas, Kadri (author)
- Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland.
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- Lahti, Jari (author)
- Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland.;Folkhalsan Res Ctr, Helsinki, Finland.
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- Gadin, Jesper R. (author)
- Karolinska Institutet
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- Backlund, Alexandra (author)
- Karolinska Institutet
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- de Faire, Ulf (author)
- Karolinska Institutet
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- Gertow, Karl (author)
- Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden.
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- Giral, Phillipe (author)
- Grp Hosp Pitie Salpetriere, AP HP, Serv Endocrinol Metab, Unites Prevent Cardiovasc, Paris, France.
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- Goel, Anuj (author)
- Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Oxford, Radcliffe Dept Med, Div Cardiovasc Med, Oxford, England.
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- Humphries, Steve E. (author)
- UCL, Inst Cardiovasc Sci, Ctr Cardiovasc Genet, London, England.
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- Kurl, Sudhir (author)
- Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio Campus, Kuopio, Finland.
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- Langenberg, Claudia (author)
- Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England.
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- Lannfelt, Lars (author)
- Uppsala universitet,Geriatrik
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- Lind, Lars (author)
- Uppsala universitet,Kardiovaskulär epidemiologi,Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.;Imperial Coll London, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England.
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- Lindgren, Cecilia C. M. (author)
- Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
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- Mannarino, Elmo (author)
- Univ Perugia, Dept Clin & Expt Med Internal Med Angiol & Arteri, Perugia, Italy.
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- Mook-Kanamori, Dennis O. (author)
- Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands.
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- Morris, Andrew P. (author)
- Univ Liverpool, Dept Biostat, Liverpool, Merseyside, England.
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- de Mutsert, Renee (author)
- Univ Helsinki, Fac Med, Dept Psychol & Logoped, Helsinki, Finland.
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- Rauramaa, Rainer (author)
- Kuopio Res Inst Exercise Med, Fdn Res Hlth Exercise & Nutr, Kuopio, Finland.;Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, Kuopio, Finland.
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- Saliba-Gustafsson, Peter (author)
- Karolinska Institutet
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- Sennblad, Bengt (author)
- Uppsala universitet,Molekylär evolution,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Med Solna, Cardiovasc Med Unit, Stockholm, Sweden
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- Smit, Andries J. (author)
- Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands.;Univ Groningen, Univ Med Ctr Groningen, Dept Med, Groningen, Netherlands.
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- Syvänen, Ann-Christine, 1950- (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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- Tremoli, Elena (author)
- Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;IRCCS, Ctr Cardiolog Monzino, Milan, Italy.
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- Veglia, Fabrizio (author)
- IRCCS, Ctr Cardiolog Monzino, Milan, Italy.
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- Zethelius, Björn (author)
- Uppsala universitet,Geriatrik
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- Bjorck, Hanna M. (author)
- Karolinska Institutet
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- Eriksson, Johan G. (author)
- Folkhalsan Res Ctr, Helsinki, Finland.;Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.;Helsinki Univ Hosp, Helsinki, Finland.;Natl Inst Hlth & Welf, Helsinki, Finland.
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- Hofman, Albert (author)
- Harvard T H Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
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Franco, Oscar H. (author)
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Watkins, Hugh (author)
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- Jukema, J. Wouter (author)
- Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.;Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
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- Florez, Jose C. (author)
- Massachusetts Gen Hosp, Diabet Unit, Boston, MA USA.;Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA USA.;Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA.
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- Wareham, Nicholas J. (author)
- Univ Cambridge, Sch Clin Med, MRC Epidemiol Unit, Cambridge, England.
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- Meigs, James B. (author)
- Broad Inst, Programs Metab & Med & Populat Genet, Cambridge, MA USA.;Harvard Med Sch, Dept Med, Cambridge, MA USA.;Massachusetts Gen Hosp, Gen Med Div, Boston, MA USA.
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- Ingelsson, Erik (author)
- Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA USA.
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- Baldassarre, Damiano (author)
- Univ Milan, Dipartimento Sci Farmacolog & Biomol, Milan, Italy.;Univ Milan, Dept Med Biotechnol & Translat Med, Milan, Italy.
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- Hamsten, Anders (author)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: Atherosclerosis. - : Elsevier BV. - 0021-9150 .- 1879-1484. ; 266, s. 196-204
- Related links:
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https://doi.org/10.1...
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https://uu.diva-port... (primary) (Raw object)
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http://www.atheroscl...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- Background and aims: Increased proinsulin relative to insulin levels have been associated with subclinical atherosclerosis (measured by carotid intima-media thickness (cIMT)) and are predictive of future cardiovascular disease (CVD), independently of established risk factors. The mechanisms linking proinsulin to atherosclerosis and CVD are unclear. A genome-wide meta-analysis has identified nine loci associated with circulating proinsulin levels. Using proinsulin-associated SNPs, we set out to use a Mendelian randomisation approach to test the hypothesis that proinsulin plays a causal role in subclinical vascular remodelling.Methods: We studied the high CVD-risk IMPROVE cohort (n = 3345), which has detailed biochemical phenotyping and repeated, state-of-the-art, high-resolution carotid ultrasound examinations. Genotyping was performed using Illumina Cardio-Metabo and Immuno arrays, which include reported proinsulin-associated loci. Participants with type 2 diabetes (n = 904) were omitted from the analysis. Linear regression was used to identify proinsulin-associated genetic variants.Results: We identified a proinsulin locus on chromosome 15 (rs8029765) and replicated it in data from 20,003 additional individuals. An 11-SNP score, including the previously identified and the chromosome 15 proinsulin-associated loci, was significantly and negatively associated with baseline IMTmean and IMTmax (the primary cIMT phenotypes) but not with progression measures. However, MR-Eggers refuted any significant effect of the proinsulin-associated 11-SNP score, and a non-pleiotropic SNP score of three variants (including rs8029765) demonstrated no effect on baseline or progression cIMT measures.Conclusions: We identified a novel proinsulin-associated locus and demonstrated that whilst proinsulin levels are associated with cIMT measures, proinsulin per se is unlikely to have a causative effect on cIMT.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- Proinsulin
- Atherosclerosis
- Intima-media-thickness
- Single nucleotide polymorphisms
- Genetic variants
- Mendelian randomisation
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Strawbridge, Ron ...
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Silveira, Angela
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den Hoed, Marcel
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Gustafsson, Stef ...
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Luan, Jian'an
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Rybin, Denis
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show more...
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Dupuis, Josee
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Li-Gao, Ruifang
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Kavousi, Maryam
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Dehghan, Abbas
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Haljas, Kadri
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Lahti, Jari
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Gadin, Jesper R.
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Backlund, Alexan ...
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de Faire, Ulf
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Gertow, Karl
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Giral, Phillipe
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Goel, Anuj
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Humphries, Steve ...
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Kurl, Sudhir
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Langenberg, Clau ...
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Lannfelt, Lars
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Lind, Lars
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Lindgren, Cecili ...
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Mannarino, Elmo
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Mook-Kanamori, D ...
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Morris, Andrew P ...
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de Mutsert, Rene ...
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Rauramaa, Rainer
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Saliba-Gustafsso ...
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Sennblad, Bengt
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Smit, Andries J.
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Syvänen, Ann-Chr ...
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Tremoli, Elena
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Veglia, Fabrizio
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Zethelius, Björn
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Bjorck, Hanna M.
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Eriksson, Johan ...
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Hofman, Albert
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Franco, Oscar H.
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Watkins, Hugh
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Jukema, J. Woute ...
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Florez, Jose C.
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Wareham, Nichola ...
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Meigs, James B.
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Ingelsson, Erik
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Baldassarre, Dam ...
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Hamsten, Anders
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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 ...
- Articles in the publication
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Atherosclerosis
- By the university
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Uppsala University
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Karolinska Institutet