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Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol.

Lange, Leslie A (author)
Hu, Youna (author)
Zhang, He (author)
show more...
Xue, Chenyi (author)
Schmidt, Ellen M (author)
Tang, Zheng-Zheng (author)
Bizon, Chris (author)
Lange, Ethan M (author)
Smith, Joshua D (author)
Turner, Emily H (author)
Jun, Goo (author)
Kang, Hyun Min (author)
Peloso, Gina (author)
Auer, Paul (author)
Li, Kuo-Ping (author)
Flannick, Jason (author)
Zhang, Ji (author)
Fuchsberger, Christian (author)
Gaulton, Kyle (author)
Lindgren, Cecilia (author)
Locke, Adam (author)
Manning, Alisa (author)
Sim, Xueling (author)
Rivas, Manuel A (author)
Holmen, Oddgeir L (author)
Gottesman, Omri (author)
Lu, Yingchang (author)
Ruderfer, Douglas (author)
Stahl, Eli A (author)
Duan, Qing (author)
Li, Yun (author)
Durda, Peter (author)
Jiao, Shuo (author)
Isaacs, Aaron (author)
Hofman, Albert (author)
Bis, Joshua C (author)
Correa, Adolfo (author)
Griswold, Michael E (author)
Jakobsdottir, Johanna (author)
Smith, Albert V (author)
Schreiner, Pamela J (author)
Feitosa, Mary F (author)
Zhang, Qunyuan (author)
Huffman, Jennifer E (author)
Crosby, Jacy (author)
Wassel, Christina L (author)
Do, Ron (author)
Franceschini, Nora (author)
Martin, Lisa W (author)
Robinson, Jennifer G (author)
Assimes, Themistocles L (author)
Crosslin, David R (author)
Rosenthal, Elisabeth A (author)
Tsai, Michael (author)
Rieder, Mark J (author)
Farlow, Deborah N (author)
Folsom, Aaron R (author)
Lumley, Thomas (author)
Fox, Ervin R (author)
Carlson, Christopher S (author)
Peters, Ulrike (author)
Jackson, Rebecca D (author)
van Duijn, Cornelia M (author)
Uitterlinden, André G (author)
Levy, Daniel (author)
Rotter, Jerome I (author)
Taylor, Herman A (author)
Gudnason, Vilmundur (author)
Siscovick, David S (author)
Fornage, Myriam (author)
Borecki, Ingrid B (author)
Hayward, Caroline (author)
Rudan, Igor (author)
Chen, Y Eugene (author)
Bottinger, Erwin P (author)
Loos, Ruth J F (author)
Sætrom, Pål (author)
Hveem, Kristian (author)
Boehnke, Michael (author)
Groop, Leif (author)
Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
McCarthy, Mark (author)
Meitinger, Thomas (author)
Ballantyne, Christie M (author)
Gabriel, Stacey B (author)
O'Donnell, Christopher J (author)
Post, Wendy S (author)
North, Kari E (author)
Reiner, Alexander P (author)
Boerwinkle, Eric (author)
Psaty, Bruce M (author)
Altshuler, David (author)
Kathiresan, Sekar (author)
Lin, Dan-Yu (author)
Jarvik, Gail P (author)
Cupples, L Adrienne (author)
Kooperberg, Charles (author)
Wilson, James G (author)
Nickerson, Deborah A (author)
Abecasis, Goncalo R (author)
Rich, Stephen S (author)
Tracy, Russell P (author)
Willer, Cristen J (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. 233-245
  • Journal article (peer-reviewed)
Abstract Subject headings
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  • Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or <2(nd) percentile). Follow-up analyses included sequencing of 1,302 additional individuals and genotype-based analysis of 52,221 individuals. We observed significant evidence of association between LDL-C and the burden of rare or low-frequency variants in PNPLA5, encoding a phospholipase-domain-containing protein, and both known and previously unidentified variants in PCSK9, LDLR and APOB, three known lipid-related genes. The effect sizes for the burden of rare variants for each associated gene were substantially higher than those observed for individual SNPs identified from GWASs. We replicated the PNPLA5 signal in an independent large-scale sequencing study of 2,084 individuals. In conclusion, this large whole-exome-sequencing study for LDL-C identified a gene not known to be implicated in LDL-C and provides unique insight into the design and analysis of similar experiments.

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)
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By the author/editor
Lange, Leslie A
Hu, Youna
Zhang, He
Xue, Chenyi
Schmidt, Ellen M
Tang, Zheng-Zhen ...
show more...
Bizon, Chris
Lange, Ethan M
Smith, Joshua D
Turner, Emily H
Jun, Goo
Kang, Hyun Min
Peloso, Gina
Auer, Paul
Li, Kuo-Ping
Flannick, Jason
Zhang, Ji
Fuchsberger, Chr ...
Gaulton, Kyle
Lindgren, Cecili ...
Locke, Adam
Manning, Alisa
Sim, Xueling
Rivas, Manuel A
Holmen, Oddgeir ...
Gottesman, Omri
Lu, Yingchang
Ruderfer, Dougla ...
Stahl, Eli A
Duan, Qing
Li, Yun
Durda, Peter
Jiao, Shuo
Isaacs, Aaron
Hofman, Albert
Bis, Joshua C
Correa, Adolfo
Griswold, Michae ...
Jakobsdottir, Jo ...
Smith, Albert V
Schreiner, Pamel ...
Feitosa, Mary F
Zhang, Qunyuan
Huffman, Jennife ...
Crosby, Jacy
Wassel, Christin ...
Do, Ron
Franceschini, No ...
Martin, Lisa W
Robinson, Jennif ...
Assimes, Themist ...
Crosslin, David ...
Rosenthal, Elisa ...
Tsai, Michael
Rieder, Mark J
Farlow, Deborah ...
Folsom, Aaron R
Lumley, Thomas
Fox, Ervin R
Carlson, Christo ...
Peters, Ulrike
Jackson, Rebecca ...
van Duijn, Corne ...
Uitterlinden, An ...
Levy, Daniel
Rotter, Jerome I
Taylor, Herman A
Gudnason, Vilmun ...
Siscovick, David ...
Fornage, Myriam
Borecki, Ingrid ...
Hayward, Carolin ...
Rudan, Igor
Chen, Y Eugene
Bottinger, Erwin ...
Loos, Ruth J F
Sætrom, Pål
Hveem, Kristian
Boehnke, Michael
Groop, Leif
McCarthy, Mark
Meitinger, Thoma ...
Ballantyne, Chri ...
Gabriel, Stacey ...
O'Donnell, Chris ...
Post, Wendy S
North, Kari E
Reiner, Alexande ...
Boerwinkle, Eric
Psaty, Bruce M
Altshuler, David
Kathiresan, Seka ...
Lin, Dan-Yu
Jarvik, Gail P
Cupples, L Adrie ...
Kooperberg, Char ...
Wilson, James G
Nickerson, Debor ...
Abecasis, Goncal ...
Rich, Stephen S
Tracy, Russell P
Willer, Cristen ...
show less...
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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