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Association of exom...
Association of exome sequences with plasma C-reactive protein levels in >9000 participants.
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Schick, Ursula M (author)
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Auer, Paul L (author)
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Bis, Joshua C (author)
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show more...
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Lin, Honghuang (author)
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Wei, Peng (author)
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Pankratz, Nathan (author)
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Lange, Leslie A (author)
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Brody, Jennifer (author)
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Stitziel, Nathan O (author)
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Kim, Daniel S (author)
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Carlson, Christopher S (author)
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Fornage, Myriam (author)
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Haessler, Jeffery (author)
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Hsu, Li (author)
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Jackson, Rebecca D (author)
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Kooperberg, Charles (author)
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Leal, Suzanne M (author)
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Psaty, Bruce M (author)
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Boerwinkle, Eric (author)
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Tracy, Russell (author)
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Ardissino, Diego (author)
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Shah, Svati (author)
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Willer, Cristen (author)
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Loos, Ruth (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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Mcpherson, Ruth (author)
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Hovingh, Kees (author)
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Reilly, Muredach (author)
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Watkins, Hugh (author)
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Girelli, Domenico (author)
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Fontanillas, Pierre (author)
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Chasman, Daniel I (author)
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Gabriel, Stacey B (author)
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Gibbs, Richard (author)
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Nickerson, Deborah A (author)
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Kathiresan, Sekar (author)
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Peters, Ulrike (author)
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Dupuis, Josée (author)
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Wilson, James G (author)
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Rich, Stephen S (author)
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Morrison, Alanna C (author)
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Benjamin, Emelia J (author)
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Gross, Myron D (author)
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Reiner, Alex P (author)
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(creator_code:org_t)
- 2014-09-03
- 2015
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 559-571
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://academic.oup...
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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
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- C-reactive protein (CRP) concentration is a heritable systemic marker of inflammation that is associated with cardiovascular disease risk. Genome-wide association studies have identified CRP-associated common variants associated in ∼25 genes. Our aims were to apply exome sequencing to (1) assess whether the candidate loci contain rare coding variants associated with CRP levels and (2) perform an exome-wide search for rare variants in novel genes associated with CRP levels. We exome-sequenced 6050 European-Americans (EAs) and 3109 African-Americans (AAs) from the NHLBI-ESP and the CHARGE consortia, and performed association tests of sequence data with measured CRP levels. In single-variant tests across candidate loci, a novel rare (minor allele frequency = 0.16%) CRP-coding variant (rs77832441-A; p.Thr59Met) was associated with 53% lower mean CRP levels (P = 2.9 × 10(-6)). We replicated the association of rs77832441 in an exome array analysis of 11 414 EAs (P = 3.0 × 10(-15)). Despite a strong effect on CRP levels, rs77832441 was not associated with inflammation-related phenotypes including coronary heart disease. We also found evidence for an AA-specific association of APOE-ε2 rs7214 with higher CRP levels. At the exome-wide significance level (P < 5.0 × 10(-8)), we confirmed associations for reported common variants of HNF1A, CRP, IL6R and TOMM40-APOE. In gene-based tests, a burden of rare/lower frequency variation in CRP in EAs (P ≤ 6.8 × 10(-4)) and in retinoic acid receptor-related orphan receptor α (RORA) in AAs (P = 1.7 × 10(-3)) were associated with CRP levels at the candidate gene level (P < 2.0 × 10(-3)). This inquiry did not elucidate novel genes, but instead demonstrated that variants distributed across the allele frequency spectrum within candidate genes contribute to CRP levels.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Schick, Ursula M
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Auer, Paul L
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Bis, Joshua C
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Lin, Honghuang
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Wei, Peng
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Pankratz, Nathan
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show more...
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Lange, Leslie A
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Brody, Jennifer
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Stitziel, Nathan ...
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Kim, Daniel S
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Carlson, Christo ...
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Fornage, Myriam
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Haessler, Jeffer ...
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Hsu, Li
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Jackson, Rebecca ...
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Kooperberg, Char ...
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Leal, Suzanne M
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Psaty, Bruce M
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Boerwinkle, Eric
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Tracy, Russell
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Ardissino, Diego
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Shah, Svati
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Willer, Cristen
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Loos, Ruth
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Melander, Olle
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Mcpherson, Ruth
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Hovingh, Kees
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Reilly, Muredach
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Watkins, Hugh
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Girelli, Domenic ...
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Fontanillas, Pie ...
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Chasman, Daniel ...
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Gabriel, Stacey ...
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Gibbs, Richard
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Nickerson, Debor ...
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Kathiresan, Seka ...
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Peters, Ulrike
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Dupuis, Josée
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Wilson, James G
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Rich, Stephen S
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Morrison, Alanna ...
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Benjamin, Emelia ...
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Gross, Myron D
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Reiner, Alex P
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show less...
- About the subject
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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
- Articles in the publication
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Human Molecular ...
- By the university
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Lund University