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Genetic architectur...
Genetic architecture of circulating lipid levels
- Article/chapterEnglish2011
Publisher, publication year, extent ...
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2011-03-30
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Springer Science and Business Media LLC,2011
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:uu-155945
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-155945URI
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https://doi.org/10.1038/ejhg.2011.21DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:122773347URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Serum concentrations of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TGs) and total cholesterol (TC) are important heritable risk factors for cardiovascular disease. Although genome-wide association studies (GWASs) of circulating lipid levels have identified numerous loci, a substantial portion of the heritability of these traits remains unexplained. Evidence of unexplained genetic variance can be detected by combining multiple independent markers into additive genetic risk scores. Such polygenic scores, constructed using results from the ENGAGE Consortium GWAS on serum lipids, were applied to predict lipid levels in an independent population-based study, the Rotterdam Study-II (RS-II). We additionally tested for evidence of a shared genetic basis for different lipid phenotypes. Finally, the polygenic score approach was used to identify an alternative genome-wide significance threshold before pathway analysis and those results were compared with those based on the classical genome-wide significance threshold. Our study provides evidence suggesting that many loci influencing circulating lipid levels remain undiscovered. Cross-prediction models suggested a small overlap between the polygenic backgrounds involved in determining LDL-C, HDL-C and TG levels. Pathway analysis utilizing the best polygenic score for TC uncovered extra information compared with using only genome-wide significant loci. These results suggest that the genetic architecture of circulating lipids involves a number of undiscovered variants with very small effects, and that increasing GWAS sample sizes will enable the identification of novel variants that regulate lipid levels.
Subject headings and genre
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serum lipids
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polygenic
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genome-wide association
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polygenic score
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pathway analysis
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MEDICINE
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MEDICIN
Added entries (persons, corporate bodies, meetings, titles ...)
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Amin, Najaf
(author)
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Isaacs, Aaron
(author)
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Jarvelin, Marjo-Riitta
(author)
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Whitfield, John B.
(author)
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Wichmann, Heinz-Erich
(author)
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Kyvik, Kirsten Ohm
(author)
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Rudan, Igor
(author)
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Gieger, Christian
(author)
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Hicks, Andrew A.
(author)
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Johansson, ÅsaUppsala universitet,Institutionen för genetik och patologi(Swepub:uu)asjoh108
(author)
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Hottenga, Jouke-Jan
(author)
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Smith, Johannes J.
(author)
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Wild, Sarah H.
(author)
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Pedersen, Nancy L.Karolinska Institutet
(author)
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Willemsen, Gonneke
(author)
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Mangino, Massimo
(author)
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Hayward, Caroline
(author)
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Uitterlinden, Andre G.
(author)
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Hofman, Albert
(author)
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Witteman, Jacqueline
(author)
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Montgomery, Grant W.
(author)
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Pietilainen, Kirsi H.
(author)
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Rantanen, Taina
(author)
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Kaprio, Jaakko
(author)
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Doering, Angela
(author)
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Pramstaller, Peter P.Karolinska Institutet
(author)
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Gyllensten, UlfUppsala universitet,Institutionen för genetik och patologi(Swepub:uu)ulfgyll
(author)
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de Geus, Eco J. C.
(author)
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Penninx, Brenda W.
(author)
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Wilson, James F.
(author)
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Rivadeneria, Fernando
(author)
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Magnusson, Patrik K. E.
(author)
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Boomsma, Dorret I.
(author)
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Spector, Tim
(author)
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Campbell, Harry
(author)
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Hoehne, Birgit
(author)
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Martin, Nicholas G.
(author)
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Oostra, Ben A.
(author)
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McCarthy, Mark
(author)
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Peltonen-Palotie, Leena
(author)
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Aulchenko, Yurii
(author)
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Visscher, Peter M.
(author)
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Ripatti, Samuli
(author)
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Janssens, A. Cecile J. W.
(author)
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van Duijn, Cornelia M.
(author)
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Uppsala universitetInstitutionen för genetik och patologi
(creator_code:org_t)
Related titles
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In:European Journal of Human Genetics: Springer Science and Business Media LLC19:7, s. 813-8191018-48131476-5438
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