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Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis

Author

Listed:
  • Luca A Lotta
  • Robert A Scott
  • Stephen J Sharp
  • Stephen Burgess
  • Jian’an Luan
  • Therese Tillin
  • Amand F Schmidt
  • Fumiaki Imamura
  • Isobel D Stewart
  • John R B Perry
  • Luke Marney
  • Albert Koulman
  • Edward D Karoly
  • Nita G Forouhi
  • Rasmus J O Sjögren
  • Erik Näslund
  • Juleen R Zierath
  • Anna Krook
  • David B Savage
  • Julian L Griffin
  • Nishi Chaturvedi
  • Aroon D Hingorani
  • Kay-Tee Khaw
  • Inês Barroso
  • Mark I McCarthy
  • Stephen O’Rahilly
  • Nicholas J Wareham
  • Claudia Langenberg

Abstract

Background: Higher circulating levels of the branched-chain amino acids (BCAAs; i.e., isoleucine, leucine, and valine) are strongly associated with higher type 2 diabetes risk, but it is not known whether this association is causal. We undertook large-scale human genetic analyses to address this question. Methods and Findings: Genome-wide studies of BCAA levels in 16,596 individuals revealed five genomic regions associated at genome-wide levels of significance (p

Suggested Citation

  • Luca A Lotta & Robert A Scott & Stephen J Sharp & Stephen Burgess & Jian’an Luan & Therese Tillin & Amand F Schmidt & Fumiaki Imamura & Isobel D Stewart & John R B Perry & Luke Marney & Albert Koulman, 2016. "Genetic Predisposition to an Impaired Metabolism of the Branched-Chain Amino Acids and Risk of Type 2 Diabetes: A Mendelian Randomisation Analysis," PLOS Medicine, Public Library of Science, vol. 13(11), pages 1-22, November.
    • Handle: RePEc:plo:pmed00:1002179
    DOI: 10.1371/journal.pmed.1002179
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    Cited by:

    1. Roderick C. Slieker & Louise A. Donnelly & Elina Akalestou & Livia Lopez-Noriega & Rana Melhem & Ayşim Güneş & Frederic Abou Azar & Alexander Efanov & Eleni Georgiadou & Hermine Muniangi-Muhitu & Mahs, 2023. "Identification of biomarkers for glycaemic deterioration in type 2 diabetes," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Rachel J. Roth Flach & Eliza Bollinger & Allan R. Reyes & Brigitte Laforest & Bethany L. Kormos & Shenping Liu & Matthew R. Reese & Luis A. Martinez Alsina & Leanne Buzon & Yuan Zhang & Bruce Bechle &, 2023. "Small molecule branched-chain ketoacid dehydrogenase kinase (BDK) inhibitors with opposing effects on BDK protein levels," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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