IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0037056.html
   My bibliography  Save this article

A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides

Author

Listed:
  • Timothy R Braun
  • Latonya F Been
  • Akhil Singhal
  • Jacob Worsham
  • Sarju Ralhan
  • Gurpreet S Wander
  • John C Chambers
  • Jaspal S Kooner
  • Christopher E Aston
  • Dharambir K Sanghera

Abstract

Recent genome-wide association scans (GWAS) and meta-analysis studies on European populations have identified many genes previously implicated in lipid regulation. Validation of these loci on different global populations is important in determining their clinical relevance, particularly for development of novel drug targets for treating and preventing diabetic dyslipidemia and coronary artery disease (CAD). In an attempt to replicate GWAS findings on a non-European sample, we examined the role of six of these loci (CELSR2-PSRC1-SORT1 rs599839; CDKN2A-2B rs1333049; BUD13-ZNF259 rs964184; ZNF259 rs12286037; CETP rs3764261; APOE-C1-C4-C2 rs4420638) in our Asian Indian cohort from the Sikh Diabetes Study (SDS) comprising 3,781 individuals (2,902 from Punjab and 879 from the US). Two of the six SNPs examined showed convincing replication in these populations of Asian Indian origin. Our study confirmed a strong association of CETP rs3764261 with high-density lipoprotein cholesterol (HDL-C) (p = 2.03×10−26). Our results also showed significant associations of two GWAS SNPs (rs964184 and rs12286037) from BUD13-ZNF259 near the APOA5-A4-C3-A1 genes with triglyceride (TG) levels in this Asian Indian cohort (rs964184: p = 1.74×10−17; rs12286037: p = 1.58×10−2). We further explored 45 SNPs in a ∼195 kb region within the chromosomal region 11q23.3 (encompassing the BUD13-ZNF259, APOA5-A4-C3-A1, and SIK3 genes) in 8,530 Asian Indians from the London Life Sciences Population (LOLIPOP) (UK) and SDS cohorts. Five more SNPs revealed significant associations with TG in both cohorts individually as well as in a joint meta-analysis. However, the strongest signal for TG remained with BUD13-ZNF259 (rs964184: p = 1.06×10−39). Future targeted deep sequencing and functional studies should enhance our understanding of the clinical relevance of these genes in dyslipidemia and hypertriglyceridemia (HTG) and, consequently, diabetes and CAD.

Suggested Citation

  • Timothy R Braun & Latonya F Been & Akhil Singhal & Jacob Worsham & Sarju Ralhan & Gurpreet S Wander & John C Chambers & Jaspal S Kooner & Christopher E Aston & Dharambir K Sanghera, 2012. "A Replication Study of GWAS-Derived Lipid Genes in Asian Indians: The Chromosomal Region 11q23.3 Harbors Loci Contributing to Triglycerides," PLOS ONE, Public Library of Science, vol. 7(5), pages 1-12, May.
    • Handle: RePEc:plo:pone00:0037056
    DOI: 10.1371/journal.pone.0037056
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0037056
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0037056&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0037056?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. David Reich & Kumarasamy Thangaraj & Nick Patterson & Alkes L. Price & Lalji Singh, 2009. "Reconstructing Indian population history," Nature, Nature, vol. 461(7263), pages 489-494, September.
    2. Peter Libby & Paul M Ridker & Göran K. Hansson, 2011. "Progress and challenges in translating the biology of atherosclerosis," Nature, Nature, vol. 473(7347), pages 317-325, May.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Qin Qin Huang & Neneh Sallah & Diana Dunca & Bhavi Trivedi & Karen A. Hunt & Sam Hodgson & Samuel A. Lambert & Elena Arciero & John Wright & Chris Griffiths & Richard C. Trembath & Harry Hemingway & M, 2022. "Transferability of genetic loci and polygenic scores for cardiometabolic traits in British Pakistani and Bangladeshi individuals," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Gyaneshwer Chaubey & Anurag Kadian & Saroj Bala & Vadlamudi Raghavendra Rao, 2015. "Genetic Affinity of the Bhil, Kol and Gond Mentioned in Epic Ramayana," PLOS ONE, Public Library of Science, vol. 10(6), pages 1-11, June.
    2. Michael Bridges & Elizabeth A Heron & Colm O'Dushlaine & Ricardo Segurado & The International Schizophrenia Consortium (ISC) & Derek Morris & Aiden Corvin & Michael Gill & Carlos Pinto, 2011. "Genetic Classification of Populations Using Supervised Learning," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-12, May.
    3. Abderrahim Nemmar & Deepa Subramaniyan & Badreldin H Ali, 2012. "Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-9, June.
    4. Kay Young McChesney, 2015. "Teaching Diversity," SAGE Open, , vol. 5(4), pages 21582440156, October.
    5. Leonardo Vallini & Carlo Zampieri & Mohamed Javad Shoaee & Eugenio Bortolini & Giulia Marciani & Serena Aneli & Telmo Pievani & Stefano Benazzi & Alberto Barausse & Massimo Mezzavilla & Michael D. Pet, 2024. "The Persian plateau served as hub for Homo sapiens after the main out of Africa dispersal," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. Rozaimi Mohamad Razali & Juan Rodriguez-Flores & Mohammadmersad Ghorbani & Haroon Naeem & Waleed Aamer & Elbay Aliyev & Ali Jubran & Andrew G. Clark & Khalid A. Fakhro & Younes Mokrab, 2021. "Thousands of Qatari genomes inform human migration history and improve imputation of Arab haplotypes," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    7. Mark S Hibbins & Matthew W Hahn, 2021. "The effects of introgression across thousands of quantitative traits revealed by gene expression in wild tomatoes," PLOS Genetics, Public Library of Science, vol. 17(11), pages 1-20, November.
    8. David B. Stern & Nathan W. Anderson & Juanita A. Diaz & Carol Eunmi Lee, 2022. "Genome-wide signatures of synergistic epistasis during parallel adaptation in a Baltic Sea copepod," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. S Justin Carlus & Saumya Sarkar & Sandeep Kumar Bansal & Vertika Singh & Kiran Singh & Rajesh Kumar Jha & Nirmala Sadasivam & Sri Revathy Sadasivam & P S Gireesha & Kumarasamy Thangaraj & Singh Rajend, 2016. "Is MTHFR 677 C>T Polymorphism Clinically Important in Polycystic Ovarian Syndrome (PCOS)? A Case-Control Study, Meta-Analysis and Trial Sequential Analysis," PLOS ONE, Public Library of Science, vol. 11(3), pages 1-15, March.
    10. Patricia Hernández-López & Miguel A. Martínez & Estefanía Peña & Myriam Cilla, 2023. "Understanding the Parameter Influence on Lesion Growth for a Mechanobiology Model of Atherosclerosis," Mathematics, MDPI, vol. 11(4), pages 1-25, February.
    11. Stephanie D. Ansley & Jeffrey T. Howard, 2021. "Dietary Intake and Elevated C-Reactive Protein Levels in US Military Veterans," IJERPH, MDPI, vol. 18(2), pages 1-15, January.
    12. Zhijun Wu & Yuqing Lou & Wei Jin & Yan Liu & Lin Lu & Guoping Lu, 2012. "The Pro12Ala Polymorphism in the Peroxisome Proliferator-Activated Receptor Gamma-2 Gene (PPARγ2) Is Associated with Increased Risk of Coronary Artery Disease: A Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(12), pages 1-14, December.
    13. Buzbas, Erkan Ozge & Verdu, Paul, 2018. "Inference on admixture fractions in a mechanistic model of recurrent admixture," Theoretical Population Biology, Elsevier, vol. 122(C), pages 149-157.
    14. Gunjan Sharma & Rakesh Tamang & Ruchira Chaudhary & Vipin Kumar Singh & Anish M Shah & Sharath Anugula & Deepa Selvi Rani & Alla G Reddy & Muthukrishnan Eaaswarkhanth & Gyaneshwer Chaubey & Lalji Sing, 2012. "Genetic Affinities of the Central Indian Tribal Populations," PLOS ONE, Public Library of Science, vol. 7(2), pages 1-8, February.
    15. David Gordon & Shailen Nandy, 2016. "The Extent, Nature and Distribution of Child Poverty in India," Indian Journal of Human Development, , vol. 10(1), pages 64-84, April.
    16. Jeffrey D. Wall & J. Fah Sathirapongsasuti & Ravi Gupta & Asif Rasheed & Radha Venkatesan & Saurabh Belsare & Ramesh Menon & Sameer Phalke & Anuradha Mittal & John Fang & Deepak Tanneeru & Manjari Des, 2023. "South Asian medical cohorts reveal strong founder effects and high rates of homozygosity," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    17. Mengying Wang & Siyue Wang & Xiaowen Wang & Junhui Wu & Yao Wu & Zijing Wang & Jiating Wang & Tao Wu & Yonghua Hu, 2020. "Carotid Intima-Media Thickness, Genetic Risk, and Ischemic Stroke: A Family-Based Study in Rural China," IJERPH, MDPI, vol. 18(1), pages 1-11, December.
    18. Todd, Megan A. & Shkolnikov, Vladimir M. & Goldman, Noreen, 2016. "Why are well-educated Muscovites more likely to survive? Understanding the biological pathways," Social Science & Medicine, Elsevier, vol. 157(C), pages 138-147.
    19. Lejla Kovacevic & Kristiina Tambets & Anne-Mai Ilumäe & Alena Kushniarevich & Bayazit Yunusbayev & Anu Solnik & Tamer Bego & Dragan Primorac & Vedrana Skaro & Andreja Leskovac & Zlatko Jakovski & Katj, 2014. "Standing at the Gateway to Europe - The Genetic Structure of Western Balkan Populations Based on Autosomal and Haploid Markers," PLOS ONE, Public Library of Science, vol. 9(8), pages 1-15, August.
    20. Tae Kyeong Kim & Sejin Jeon & Seonjun Park & Seong-Keun Sonn & Seungwoon Seo & Joowon Suh & Jing Jin & Hyae Yon Kweon & Sinai Kim & Shin Hye Moon & Okhee Kweon & Bon-Hyeock Koo & Nayoung Kim & Hae-Ock, 2022. "2′–5′ oligoadenylate synthetase‑like 1 (OASL1) protects against atherosclerosis by maintaining endothelial nitric oxide synthase mRNA stability," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0037056. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.