Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

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Peloso, Gina M (author)

Association of low-frequency and rare coding-sequence variants with blood lipids and coronary heart disease in 56,000 whites and blacks.

Article/chapterEnglish2014

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Elsevier BV,2014

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LIBRIS-ID:oai:lup.lub.lu.se:5867df04-a8e1-436a-ac9a-3428a708efe4
https://lup.lub.lu.se/record/4335257URI
https://doi.org/10.1016/j.ajhg.2014.01.009DOI

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Language:English
Summary in:English

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Subject category:art swepub-publicationtype
Subject category:ref swepub-contenttype

Notes

Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncertain whether the PCSK9 example represents a paradigm or an isolated exception. We used the "Exome Array" to genotype >200,000 low-frequency and rare coding sequence variants across the genome in 56,538 individuals (42,208 European ancestry [EA] and 14,330 African ancestry [AA]) and tested these variants for association with LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. Although we did not identify new genes associated with LDL-C, we did identify four low-frequency (frequencies between 0.1% and 2%) variants (ANGPTL8 rs145464906 [c.361C>T; p.Gln121(∗)], PAFAH1B2 rs186808413 [c.482C>T; p.Ser161Leu], COL18A1 rs114139997 [c.331G>A; p.Gly111Arg], and PCSK7 rs142953140 [c.1511G>A; p.Arg504His]) with large effects on HDL-C and/or triglycerides. None of these four variants was associated with risk for CHD, suggesting that examples of low-frequency coding variants with robust effects on both lipids and CHD will be limited.

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Auer, Paul L (author)
Bis, Joshua C (author)
Voorman, Arend (author)
Morrison, Alanna C (author)
Stitziel, Nathan O (author)
Brody, Jennifer A (author)
Khetarpal, Sumeet A (author)
Crosby, Jacy R (author)
Fornage, Myriam (author)
Isaacs, Aaron (author)
Jakobsdottir, Johanna (author)
Feitosa, Mary F (author)
Davies, Gail (author)
Huffman, Jennifer E (author)
Manichaikul, Ani (author)
Davis, Brian (author)
Lohman, Kurt (author)
Joon, Aron Y (author)
Smith, Albert V (author)
Grove, Megan L (author)
Zanoni, Paolo (author)
Redon, Valeska (author)
Demissie, Serkalem (author)
Lawson, Kim (author)
Peters, Ulrike (author)
Carlson, Christopher (author)
Jackson, Rebecca D (author)
Ryckman, Kelli K (author)
Mackey, Rachel H (author)
Robinson, Jennifer G (author)
Siscovick, David S (author)
Schreiner, Pamela J (author)
Mychaleckyj, Josyf C (author)
Pankow, James S (author)
Hofman, Albert (author)
Uitterlinden, Andre G (author)
Harris, Tamara B (author)
Taylor, Kent D (author)
Stafford, Jeanette M (author)
Reynolds, Lindsay M (author)
Marioni, Riccardo E (author)
Dehghan, Abbas (author)
Franco, Oscar H (author)
Patel, Aniruddh P (author)
Lu, Yingchang (author)
Hindy, GeorgeLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)med-ghu (author)
Gottesman, Omri (author)
Bottinger, Erwin P (author)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (author)
Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor (author)
Loos, Ruth J F (author)
Duga, Stefano (author)
Merlini, Piera Angelica (author)
Farrall, Martin (author)
Goel, Anuj (author)
Asselta, Rosanna (author)
Girelli, Domenico (author)
Martinelli, Nicola (author)
Shah, Svati H (author)
Kraus, William E (author)
Li, Mingyao (author)
Rader, Daniel J (author)
Reilly, Muredach P (author)
McPherson, Ruth (author)
Watkins, Hugh (author)
Ardissino, Diego (author)
Zhang, Qunyuan (author)
Wang, Judy (author)
Tsai, Michael Y (author)
Taylor, Herman A (author)
Correa, Adolfo (author)
Griswold, Michael E (author)
Lange, Leslie A (author)
Starr, John M (author)
Rudan, Igor (author)
Eiriksdottir, Gudny (author)
Launer, Lenore J (author)
Ordovas, Jose M (author)
Levy, Daniel (author)
Chen, Y-D Ida (author)
Reiner, Alexander P (author)
Hayward, Caroline (author)
Polasek, Ozren (author)
Deary, Ian J (author)
Borecki, Ingrid B (author)
Liu, Yongmei (author)
Gudnason, Vilmundur (author)
Wilson, James G (author)
van Duijn, Cornelia M (author)
Kooperberg, Charles (author)
Rich, Stephen S (author)
Psaty, Bruce M (author)
Rotter, Jerome I (author)
O'Donnell, Christopher J (author)
Rice, Kenneth (author)
Boerwinkle, Eric (author)
Kathiresan, Sekar (author)
Cupples, L Adrienne (author)
Diabetes - kardiovaskulär sjukdomForskargrupper vid Lunds universitet (creator_code:org_t)

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In:American Journal of Human Genetics: Elsevier BV94:2, s. 223-2320002-9297

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By the author/editor: Peloso, Gina M; Auer, Paul L; Bis, Joshua C; Voorman, Arend; Morrison, Alanna ...; Stitziel, Nathan ...; show more...; Brody, Jennifer ...; Khetarpal, Sumee ...; Crosby, Jacy R; Fornage, Myriam; Isaacs, Aaron; Jakobsdottir, Jo ...; Feitosa, Mary F; Davies, Gail; Huffman, Jennife ...; Manichaikul, Ani; Davis, Brian; Lohman, Kurt; Joon, Aron Y; Smith, Albert V; Grove, Megan L; Zanoni, Paolo; Redon, Valeska; Demissie, Serkal ...; Lawson, Kim; Peters, Ulrike; Carlson, Christo ...; Jackson, Rebecca ...; Ryckman, Kelli K; Mackey, Rachel H; Robinson, Jennif ...; Siscovick, David ...; Schreiner, Pamel ...; Mychaleckyj, Jos ...; Pankow, James S; Hofman, Albert; Uitterlinden, An ...; Harris, Tamara B; Taylor, Kent D; Stafford, Jeanet ...; Reynolds, Lindsa ...; Marioni, Riccard ...; Dehghan, Abbas; Franco, Oscar H; Patel, Aniruddh ...; Lu, Yingchang; Hindy, George; Gottesman, Omri; Bottinger, Erwin ...; Melander, Olle; Orho-Melander, M ...; Loos, Ruth J F; Duga, Stefano; Merlini, Piera A ...; Farrall, Martin; Goel, Anuj; Asselta, Rosanna; Girelli, Domenic ...; Martinelli, Nico ...; Shah, Svati H; Kraus, William E; Li, Mingyao; Rader, Daniel J; Reilly, Muredach ...; McPherson, Ruth; Watkins, Hugh; Ardissino, Diego; Zhang, Qunyuan; Wang, Judy; Tsai, Michael Y; Taylor, Herman A; Correa, Adolfo; Griswold, Michae ...; Lange, Leslie A; Starr, John M; Rudan, Igor; Eiriksdottir, Gu ...; Launer, Lenore J; Ordovas, Jose M; Levy, Daniel; Chen, Y-D Ida; Reiner, Alexande ...; Hayward, Carolin ...; Polasek, Ozren; Deary, Ian J; Borecki, Ingrid ...; Liu, Yongmei; Gudnason, Vilmun ...; Wilson, James G; van Duijn, Corne ...; Kooperberg, Char ...; Rich, Stephen S; Psaty, Bruce M; Rotter, Jerome I; O'Donnell, Chris ...; Rice, Kenneth; Boerwinkle, Eric; Kathiresan, Seka ...; Cupples, L Adrie ...; show less...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

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By the university: Lund University

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