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

Peloso, Gina M (author)
Auer, Paul L (author)
Bis, Joshua C (author)
show more...
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, George (author)
Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
Gottesman, Omri (author)
Bottinger, Erwin P (author)
Melander, Olle (author)
Lund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups
Orho-Melander, Marju (author)
Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups
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)
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 (creator_code:org_t)
Elsevier BV, 2014
2014
English.
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 94:2, s. 223-232
  • Journal article (peer-reviewed)
Abstract Subject headings
Close  
  • 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.

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
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 ...
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About the subject
MEDICAL AND HEALTH SCIENCES
MEDICAL AND HEAL ...
and Basic Medicine
and Medical Genetics
Articles in the publication
American Journal ...
By the university
Lund University

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