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Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained

Author

Listed:
  • Ying Wu
  • Lindsay L Waite
  • Anne U Jackson
  • Wayne H-H Sheu
  • Steven Buyske
  • Devin Absher
  • Donna K Arnett
  • Eric Boerwinkle
  • Lori L Bonnycastle
  • Cara L Carty
  • Iona Cheng
  • Barbara Cochran
  • Damien C Croteau-Chonka
  • Logan Dumitrescu
  • Charles B Eaton
  • Nora Franceschini
  • Xiuqing Guo
  • Brian E Henderson
  • Lucia A Hindorff
  • Eric Kim
  • Leena Kinnunen
  • Pirjo Komulainen
  • Wen-Jane Lee
  • Loic Le Marchand
  • Yi Lin
  • Jaana Lindström
  • Oddgeir Lingaas-Holmen
  • Sabrina L Mitchell
  • Narisu Narisu
  • Jennifer G Robinson
  • Fred Schumacher
  • Alena Stančáková
  • Jouko Sundvall
  • Yun-Ju Sung
  • Amy J Swift
  • Wen-Chang Wang
  • Lynne Wilkens
  • Tom Wilsgaard
  • Alicia M Young
  • Linda S Adair
  • Christie M Ballantyne
  • Petra Bůžková
  • Aravinda Chakravarti
  • Francis S Collins
  • David Duggan
  • Alan B Feranil
  • Low-Tone Ho
  • Yi-Jen Hung
  • Steven C Hunt
  • Kristian Hveem
  • Jyh-Ming J Juang
  • Antero Y Kesäniemi
  • Johanna Kuusisto
  • Markku Laakso
  • Timo A Lakka
  • I-Te Lee
  • Mark F Leppert
  • Tara C Matise
  • Leena Moilanen
  • Inger Njølstad
  • Ulrike Peters
  • Thomas Quertermous
  • Rainer Rauramaa
  • Jerome I Rotter
  • Jouko Saramies
  • Jaakko Tuomilehto
  • Matti Uusitupa
  • Tzung-Dau Wang
  • Michael Boehnke
  • Christopher A Haiman
  • Yii-Der I Chen
  • Charles Kooperberg
  • Themistocles L Assimes
  • Dana C Crawford
  • Chao A Hsiung
  • Kari E North
  • Karen L Mohlke

Abstract

Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P

Suggested Citation

  • Ying Wu & Lindsay L Waite & Anne U Jackson & Wayne H-H Sheu & Steven Buyske & Devin Absher & Donna K Arnett & Eric Boerwinkle & Lori L Bonnycastle & Cara L Carty & Iona Cheng & Barbara Cochran & Damie, 2013. "Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained," PLOS Genetics, Public Library of Science, vol. 9(3), pages 1-16, March.
    • Handle: RePEc:plo:pgen00:1003379
    DOI: 10.1371/journal.pgen.1003379
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    Cited by:

    1. Martijn van de Bunt & Adrian Cortes & IGAS Consortium & Matthew A Brown & Andrew P Morris & Mark I McCarthy, 2015. "Evaluating the Performance of Fine-Mapping Strategies at Common Variant GWAS Loci," PLOS Genetics, Public Library of Science, vol. 11(9), pages 1-14, September.

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