The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Photo: KG Pressfoto

Marju Orho-Melander


Photo: KG Pressfoto

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


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

Summary, in English

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.


  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







American Journal of Human Genetics





Document type

Journal article


Cell Press


  • Medical Genetics



Research group

  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Hypertension


  • ISSN: 0002-9297