IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0020640.html
   My bibliography  Save this article

Implications of Central Obesity-Related Variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on Quantitative Metabolic Traits in Adult Danes

Author

Listed:
  • Dorthe S Bille
  • Karina Banasik
  • Johanne M Justesen
  • Camilla H Sandholt
  • Annelli Sandbæk
  • Torsten Lauritzen
  • Torben Jørgensen
  • Daniel R Witte
  • Jens-Christian Holm
  • Torben Hansen
  • Oluf Pedersen

Abstract

Background: Two meta-analyses of genome-wide association studies (GWAS) have suggested that four variants: rs2605100 in lysophospholipase-like 1 (LYPLAL1), rs10146997 in neuroxin 3 (NRXN3), rs545854 in methionine sulfoxide reductase A (MSRA), and rs987237 in transcription factor activating enhancer-binding protein 2 beta (TFAP2B) associate with measures of central obesity. Methodology/Principal Findings: The four variants were genotyped in Danish individuals using KASPar®. Quantitative metabolic traits were examined in a population-based sample (n = 6,038) and WC and BMI were furthermore analyzed in a combined study sample (n = 13,507). Case-control studies of diabetes and adiposity included 15,326 individuals. The major G-allele of LYPLAL1 rs2605100 associated with increased fasting serum triglyceride concentrations (per allele effect (β) = 3%(1;5(95%CI)), padditive = 2.7×10−3), an association driven by the male gender (pinteraction = 0.02). The same allele associated with increased fasting serum insulin concentrations (β = 3%(1;5), padditive = 2.5×10−3) and increased insulin resistance (HOMA-IR) (β = 4%(1;6), padditive = 1.5×10−3). The minor G-allele of rs10146997 in NRXN3 associated with increased WC among women (β = 0.55cm (0.20;0.89), padditive = 1.7×10−3, pinteraction = 1.0×10−3), but showed no associations with obesity related metabolic traits. The MSRA rs545854 and TFAP2B rs987237 showed nominal associations with central obesity; however, no underlying metabolic phenotypes became obvious, when investigating quantitative metabolic traits. None of the variants influenced the prevalence of type 2 diabetes. Conclusion/Significance: We demonstrate that several of the central obesity-associated variants in LYPLAL1, NRXN3, MSRA, and TFAP2B associate with metabolic and anthropometric traits in Danish adults. However, analyses were made without adjusting for multiple testing, and further studies are needed to confirm the putative role of LYPLAL1, NRXN3, MSRA, and TFAP2B in the pathophysiology of obesity.

Suggested Citation

  • Dorthe S Bille & Karina Banasik & Johanne M Justesen & Camilla H Sandholt & Annelli Sandbæk & Torsten Lauritzen & Torben Jørgensen & Daniel R Witte & Jens-Christian Holm & Torben Hansen & Oluf Pederse, 2011. "Implications of Central Obesity-Related Variants in LYPLAL1, NRXN3, MSRA, and TFAP2B on Quantitative Metabolic Traits in Adult Danes," PLOS ONE, Public Library of Science, vol. 6(6), pages 1-7, June.
  • Handle: RePEc:plo:pone00:0020640
    DOI: 10.1371/journal.pone.0020640
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0020640
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0020640&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0020640?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. Cecilia M Lindgren & Iris M Heid & Joshua C Randall & Claudia Lamina & Valgerdur Steinthorsdottir & Lu Qi & Elizabeth K Speliotes & Gudmar Thorleifsson & Cristen J Willer & Blanca M Herrera & Anne U J, 2009. "Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-13, June.
    2. Nancy L Heard-Costa & M Carola Zillikens & Keri L Monda & Åsa Johansson & Tamara B Harris & Mao Fu & Talin Haritunians & Mary F Feitosa & Thor Aspelund & Gudny Eiriksdottir & Melissa Garcia & Lenore J, 2009. "NRXN3 Is a Novel Locus for Waist Circumference: A Genome-Wide Association Study from the CHARGE Consortium," PLOS Genetics, Public Library of Science, vol. 5(6), pages 1-9, June.
    Full references (including those not matched with items on IDEAS)

    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. Nicole M Warrington & Yan Yan Wu & Craig E Pennell & Julie A Marsh & Lawrence J Beilin & Lyle J Palmer & Stephen J Lye & Laurent Briollais, 2013. "Modelling BMI Trajectories in Children for Genetic Association Studies," PLOS ONE, Public Library of Science, vol. 8(1), pages 1-12, January.
    2. Zari Dastani & Marie-France Hivert & Nicholas Timpson & John R B Perry & Xin Yuan & Robert A Scott & Peter Henneman & Iris M Heid & Jorge R Kizer & Leo-Pekka Lyytikäinen & Christian Fuchsberger & Tosh, 2012. "Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals," PLOS Genetics, Public Library of Science, vol. 8(3), pages 1-23, March.
    3. Joshua C Randall & Thomas W Winkler & Zoltán Kutalik & Sonja I Berndt & Anne U Jackson & Keri L Monda & Tuomas O Kilpeläinen & Tõnu Esko & Reedik Mägi & Shengxu Li & Tsegaselassie Workalemahu & Mary F, 2013. "Sex-stratified Genome-wide Association Studies Including 270,000 Individuals Show Sexual Dimorphism in Genetic Loci for Anthropometric Traits," PLOS Genetics, Public Library of Science, vol. 9(6), pages 1-19, June.
    4. Yvonne V Louwers & Nigel W Rayner & Blanca M Herrera & Lisette Stolk & Christopher J Groves & Thomas M Barber & Andre G Uitterlinden & Stephen Franks & Joop S E Laven & Mark I McCarthy, 2014. "BMI-Associated Alleles Do Not Constitute Risk Alleles for Polycystic Ovary Syndrome Independently of BMI: A Case-Control Study," PLOS ONE, Public Library of Science, vol. 9(1), pages 1-7, January.
    5. Merete Ellingjord-Dale & Nikos Papadimitriou & Michail Katsoulis & Chew Yee & Niki Dimou & Dipender Gill & Dagfinn Aune & Jue-Sheng Ong & Stuart MacGregor & Benjamin Elsworth & Sarah J Lewis & Richard, 2021. "Coffee consumption and risk of breast cancer: A Mendelian randomization study," PLOS ONE, Public Library of Science, vol. 16(1), pages 1-15, January.
    6. Claire L. Simpson & Aaron J. Goldenberg & Rob Culverhouse & Denise Daley & Robert P. Igo & Gail P. Jarvik & Diptasri M. Mandal & Deborah Mascalzoni & Courtney Gray Montgomery & Brandon L. Pierce & Ros, 2014. "Practical Barriers and Ethical Challenges in Genetic Data Sharing," IJERPH, MDPI, vol. 11(8), pages 1-16, August.
    7. Li-Jun Tan & Hu Zhu & Hao He & Ke-Hao Wu & Jian Li & Xiang-Ding Chen & Ji-Gang Zhang & Hui Shen & Qing Tian & Marie Krousel-Wood & Christopher J Papasian & Claude Bouchard & Louis Pérusse & Hong-Wen D, 2014. "Replication of 6 Obesity Genes in a Meta-Analysis of Genome-Wide Association Studies from Diverse Ancestries," PLOS ONE, Public Library of Science, vol. 9(5), pages 1-14, May.
    8. Sofus C Larsen & Lars Ängquist & Max Moldovan & Ville Huikari & Sylvain Sebert & Alana Cavadino & Tarunveer Singh Ahluwalia & Tea Skaaby & Allan Linneberg & Lise Lotte N Husemoen & Ulla Toft & Oluf Pe, 2016. "Serum 25-Hydroxyvitamin D Status and Longitudinal Changes in Weight and Waist Circumference: Influence of Genetic Predisposition to Adiposity," PLOS ONE, Public Library of Science, vol. 11(4), pages 1-18, April.

    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:pone00:0020640. 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.