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Identification of t...
Identification of the BCAR1-CFDP1-TMEM170A Locus as a Determinant of Carotid Intima-Media Thickness and Coronary Artery Disease Risk
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- Gertow, Karl (author)
- Karolinska Institutet
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- Sennblad, Bengt (author)
- Karolinska Institutet
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- Strawbridge, Rona J. (author)
- Karolinska Institutet
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- Oehrvik, John (author)
- Karolinska Institutet
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Zabaneh, Delilah (author)
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Shah, Sonia (author)
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Veglia, Fabrizio (author)
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- Fava, Cristiano (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
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Kavousi, Maryam (author)
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McLachlan, Stela (author)
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Kivimaeki, Mika (author)
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Bolton, Jennifer L. (author)
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Folkersen, Lasse (author)
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- Gigante, Bruna (author)
- Karolinska Institutet
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- Leander, Karin (author)
- Karolinska Institutet
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Vikstrom, Max (author)
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Larsson, Malin (author)
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- Silveira, Angela (author)
- Karolinska Institutet
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Deanfield, John (author)
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Voight, Benjamin F. (author)
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Fontanillas, Pierre (author)
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- Sabater-Lleal, Maria (author)
- Karolinska Institutet
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Colombo, Gualtiero I. (author)
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Kumari, Meena (author)
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Langenberg, Claudia (author)
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Wareham, Nick J. (author)
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- Uitterlinden, Andre G. (author)
- Karolinska Institutet
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Gabrielsen, Anders (author)
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- Hedin, Ulf (author)
- Karolinska Institutet
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- Franco-Cereceda, Anders (author)
- Karolinska Institutet
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Nyyssonen, Kristiina (author)
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Rauramaa, Rainer (author)
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Tuomainen, Tomi-Pekka (author)
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Savonen, Kai (author)
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Smit, Andries J. (author)
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Giral, Philippe (author)
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Mannarino, Elmo (author)
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Robertson, Christine M. (author)
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Talmud, Philippa J. (author)
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- Hedblad, Bo (author)
- Lund University,Lunds universitet,Kardiovaskulär forskning - epidemiologi,Forskargrupper vid Lunds universitet,Cardiovascular Research - Epidemiology,Lund University Research Groups
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Hofman, Albert (author)
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Erdmann, Jeanette (author)
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Reilly, Muredach P. (author)
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O'Donnell, Christopher J. (author)
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Farrall, Martin (author)
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Clarke, Robert (author)
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Franzosi, Maria Grazia (author)
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Seedorf, Udo (author)
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- Syvänen, Ann-Christine (author)
- Uppsala universitet,Molekylär medicin,Science for Life Laboratory, SciLifeLab
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Hansson, Goran K. (author)
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- Eriksson, Per (author)
- Karolinska Institutet
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Samani, Nilesh J. (author)
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Watkins, Hugh (author)
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Price, Jacqueline F. (author)
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Hingorani, Aroon D. (author)
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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
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Witteman, Jacqueline C. M. (author)
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Baldassarre, Damiano (author)
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Tremoli, Elena (author)
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- de Faire, Ulf (author)
- Karolinska Institutet
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Humphries, Steve E. (author)
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- Hamsten, Anders (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2012
- 2012
- English.
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In: Circulation: Cardiovascular Genetics. - 1942-325X .- 1942-3268. ; 5:6, s. 656-665
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- Background-Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse. Methods and Results-To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMTmean, IMTmax, and IMTmean-max), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11 590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75x10(-7) for IMTmax; replication P=7.24x10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53x10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83x10(-4), n= 82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138). Conclusions-This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent. (Circ Cardiovasc Genet. 2012;5:656-665.)
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- atherosclerosis
- carotid intima-media thickness
- coronary artery
- disease
- genetics
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Gertow, Karl
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Sennblad, Bengt
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Strawbridge, Ron ...
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Oehrvik, John
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Zabaneh, Delilah
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Shah, Sonia
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show more...
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Veglia, Fabrizio
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Fava, Cristiano
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Kavousi, Maryam
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McLachlan, Stela
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Kivimaeki, Mika
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Bolton, Jennifer ...
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Folkersen, Lasse
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Gigante, Bruna
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Leander, Karin
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Vikstrom, Max
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Larsson, Malin
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Silveira, Angela
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Deanfield, John
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Voight, Benjamin ...
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Fontanillas, Pie ...
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Sabater-Lleal, M ...
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Colombo, Gualtie ...
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Kumari, Meena
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Langenberg, Clau ...
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Wareham, Nick J.
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Uitterlinden, An ...
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Gabrielsen, Ande ...
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Hedin, Ulf
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Franco-Cereceda, ...
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Nyyssonen, Krist ...
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Rauramaa, Rainer
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Tuomainen, Tomi- ...
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Savonen, Kai
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Smit, Andries J.
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Giral, Philippe
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Mannarino, Elmo
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Robertson, Chris ...
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Talmud, Philippa ...
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Hedblad, Bo
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Hofman, Albert
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Erdmann, Jeanett ...
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Reilly, Muredach ...
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O'Donnell, Chris ...
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Farrall, Martin
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Clarke, Robert
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Franzosi, Maria ...
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Seedorf, Udo
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Syvänen, Ann-Chr ...
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Hansson, Goran K ...
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Eriksson, Per
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Samani, Nilesh J ...
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Watkins, Hugh
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Price, Jacquelin ...
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Hingorani, Aroon ...
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Melander, Olle
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Witteman, Jacque ...
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Baldassarre, Dam ...
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Tremoli, Elena
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de Faire, Ulf
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Humphries, Steve ...
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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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Circulation: Car ...
- By the university
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Lund University
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Uppsala University
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Karolinska Institutet