IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31625-5.html
   My bibliography  Save this article

Variance-quantitative trait loci enable systematic discovery of gene-environment interactions for cardiometabolic serum biomarkers

Author

Listed:
  • Kenneth E. Westerman

    (Massachusetts General Hospital
    Broad Institute of Harvard and MIT
    Harvard Medical School)

  • Timothy D. Majarian

    (Broad Institute of Harvard and MIT)

  • Franco Giulianini

    (Brigham and Women’s Hospital)

  • Dong-Keun Jang

    (Broad Institute of Harvard and MIT)

  • Jenkai Miao

    (Boston Children’s Hospital)

  • Jose C. Florez

    (Broad Institute of Harvard and MIT
    Harvard Medical School
    Massachusetts General Hospital)

  • Han Chen

    (The University of Texas Health Science Center at Houston
    The University of Texas Health Science Center at Houston)

  • Daniel I. Chasman

    (Brigham and Women’s Hospital
    Brigham and Women’s Hospital
    Medical and Population Genetics Program, Broad Institute
    Harvard T.H. Chan School of Public Health)

  • Miriam S. Udler

    (Broad Institute of Harvard and MIT
    Harvard Medical School
    Massachusetts General Hospital)

  • Alisa K. Manning

    (Massachusetts General Hospital
    Broad Institute of Harvard and MIT
    Harvard Medical School)

  • Joanne B. Cole

    (Broad Institute of Harvard and MIT
    Boston Children’s Hospital
    Massachusetts General Hospital)

Abstract

Gene-environment interactions represent the modification of genetic effects by environmental exposures and are critical for understanding disease and informing personalized medicine. These often induce differential phenotypic variance across genotypes; these variance-quantitative trait loci can be prioritized in a two-stage interaction detection strategy to greatly reduce the computational and statistical burden and enable testing of a broader range of exposures. We perform genome-wide variance-quantitative trait locus analysis for 20 serum cardiometabolic biomarkers by multi-ancestry meta-analysis of 350,016 unrelated participants in the UK Biobank, identifying 182 independent locus-biomarker pairs (p

Suggested Citation

  • Kenneth E. Westerman & Timothy D. Majarian & Franco Giulianini & Dong-Keun Jang & Jenkai Miao & Jose C. Florez & Han Chen & Daniel I. Chasman & Miriam S. Udler & Alisa K. Manning & Joanne B. Cole, 2022. "Variance-quantitative trait loci enable systematic discovery of gene-environment interactions for cardiometabolic serum biomarkers," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31625-5
    DOI: 10.1038/s41467-022-31625-5
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31625-5
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-31625-5?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. Leyao Wang & William Murk & Andrew T DeWan, 2015. "Genome-Wide Gene by Environment Interaction Analysis Identifies Common SNPs at 17q21.2 that Are Associated with Increased Body Mass Index Only among Asthmatics," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-14, December.
    2. Clare Bycroft & Colin Freeman & Desislava Petkova & Gavin Band & Lloyd T. Elliott & Kevin Sharp & Allan Motyer & Damjan Vukcevic & Olivier Delaneau & Jared O’Connell & Adrian Cortes & Samantha Welsh &, 2018. "The UK Biobank resource with deep phenotyping and genomic data," Nature, Nature, vol. 562(7726), pages 203-209, October.
    3. Jian Yang & Ruth J. F. Loos & Joseph E. Powell & Sarah E. Medland & Elizabeth K. Speliotes & Daniel I. Chasman & Lynda M. Rose & Gudmar Thorleifsson & Valgerdur Steinthorsdottir & Reedik Mägi & Lindsa, 2012. "FTO genotype is associated with phenotypic variability of body mass index," Nature, Nature, vol. 490(7419), pages 267-272, October.
    4. Thomas W Winkler & Anne E Justice & L Adrienne Cupples & Florian Kronenberg & Zoltán Kutalik & Iris M Heid & the GIANT consortium, 2017. "Approaches to detect genetic effects that differ between two strata in genome-wide meta-analyses: Recommendations based on a systematic evaluation," PLOS ONE, Public Library of Science, vol. 12(7), pages 1-23, July.
    5. Michael Francis & Changwei Li & Yitang Sun & Jingqi Zhou & Xiang Li & J Thomas Brenna & Kaixiong Ye, 2021. "Genome-wide association study of fish oil supplementation on lipid traits in 81,246 individuals reveals new gene-diet interaction loci," PLOS Genetics, Public Library of Science, vol. 17(3), pages 1-20, March.
    6. Mathias Rask-Andersen & Torgny Karlsson & Weronica E Ek & Åsa Johansson, 2017. "Gene-environment interaction study for BMI reveals interactions between genetic factors and physical activity, alcohol consumption and socioeconomic status," PLOS Genetics, Public Library of Science, vol. 13(9), pages 1-20, September.
    7. Guillaume Paré & Nancy R Cook & Paul M Ridker & Daniel I Chasman, 2010. "On the Use of Variance per Genotype as a Tool to Identify Quantitative Trait Interaction Effects: A Report from the Women's Genome Health Study," PLOS Genetics, Public Library of Science, vol. 6(6), pages 1-10, June.
    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. Peter Zhukovsky & Earvin S. Tio & Gillian Coughlan & David A. Bennett & Yanling Wang & Timothy J. Hohman & Diego A. Pizzagalli & Benoit H. Mulsant & Aristotle N. Voineskos & Daniel Felsky, 2024. "Genetic influences on brain and cognitive health and their interactions with cardiovascular conditions and depression," Nature Communications, Nature, vol. 15(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. Kathryn E. Kemper & Julia Sidorenko & Huanwei Wang & Ben J. Hayes & Naomi R. Wray & Loic Yengo & Matthew C. Keller & Michael Goddard & Peter M. Visscher, 2024. "Genetic influence on within-person longitudinal change in anthropometric traits in the UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. James P. Pirruccello & Paolo Achille & Seung Hoan Choi & Joel T. Rämö & Shaan Khurshid & Mahan Nekoui & Sean J. Jurgens & Victor Nauffal & Shinwan Kany & Kenney Ng & Samuel F. Friedman & Puneet Batra , 2024. "Deep learning of left atrial structure and function provides link to atrial fibrillation risk," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Meghana Pagadala & Timothy J. Sears & Victoria H. Wu & Eva Pérez-Guijarro & Hyo Kim & Andrea Castro & James V. Talwar & Cristian Gonzalez-Colin & Steven Cao & Benjamin J. Schmiedel & Shervin Goudarzi , 2023. "Germline modifiers of the tumor immune microenvironment implicate drivers of cancer risk and immunotherapy response," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    4. Matteo Di Scipio & Mohammad Khan & Shihong Mao & Michael Chong & Conor Judge & Nazia Pathan & Nicolas Perrot & Walter Nelson & Ricky Lali & Shuang Di & Robert Morton & Jeremy Petch & Guillaume Paré, 2023. "A versatile, fast and unbiased method for estimation of gene-by-environment interaction effects on biobank-scale datasets," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    5. Jacob Joseph & Chang Liu & Qin Hui & Krishna Aragam & Zeyuan Wang & Brian Charest & Jennifer E. Huffman & Jacob M. Keaton & Todd L. Edwards & Serkalem Demissie & Luc Djousse & Juan P. Casas & J. Micha, 2022. "Genetic architecture of heart failure with preserved versus reduced ejection fraction," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Vincent Michaud & Eulalie Lasseaux & David J. Green & Dave T. Gerrard & Claudio Plaisant & Tomas Fitzgerald & Ewan Birney & Benoît Arveiler & Graeme C. Black & Panagiotis I. Sergouniotis, 2022. "The contribution of common regulatory and protein-coding TYR variants to the genetic architecture of albinism," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    7. Dick Schijven & Sourena Soheili-Nezhad & Simon E. Fisher & Clyde Francks, 2024. "Exome-wide analysis implicates rare protein-altering variants in human handedness," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    8. Lili Liu & Atlas Khan & Elena Sanchez-Rodriguez & Francesca Zanoni & Yifu Li & Nicholas Steers & Olivia Balderes & Junying Zhang & Priya Krithivasan & Robert A. LeDesma & Clara Fischman & Scott J. Heb, 2022. "Genetic regulation of serum IgA levels and susceptibility to common immune, infectious, kidney, and cardio-metabolic traits," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Sylvia Hartmann & Summaira Yasmeen & Benjamin M. Jacobs & Spiros Denaxas & Munir Pirmohamed & Eric R. Gamazon & Mark J. Caulfield & Harry Hemingway & Maik Pietzner & Claudia Langenberg, 2023. "ADRA2A and IRX1 are putative risk genes for Raynaud’s phenomenon," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    10. Mit Shah & Marco H. A. Inácio & Chang Lu & Pierre-Raphaël Schiratti & Sean L. Zheng & Adam Clement & Antonio Marvao & Wenjia Bai & Andrew P. King & James S. Ware & Martin R. Wilkins & Johanna Mielke &, 2023. "Environmental and genetic predictors of human cardiovascular ageing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    11. Mathias Seviiri & Matthew H. Law & Jue-Sheng Ong & Puya Gharahkhani & Pierre Fontanillas & Catherine M. Olsen & David C. Whiteman & Stuart MacGregor, 2022. "A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    12. Zhening Liu & Hangkai Huang & Jiarong Xie & Yingying Xu & Chengfu Xu, 2024. "Circulating fatty acids and risk of hepatocellular carcinoma and chronic liver disease mortality in the UK Biobank," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    13. Junqing Xie & Shuo Feng & Xintong Li & Ester Gea-Mallorquí & Albert Prats-Uribe & Dani Prieto-Alhambra, 2022. "Comparative effectiveness of the BNT162b2 and ChAdOx1 vaccines against Covid-19 in people over 50," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    14. Rongtao Jiang & Stephanie Noble & Matthew Rosenblatt & Wei Dai & Jean Ye & Shu Liu & Shile Qi & Vince D. Calhoun & Jing Sui & Dustin Scheinost, 2024. "The brain structure, inflammatory, and genetic mechanisms mediate the association between physical frailty and depression," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    15. Erik Schoenmakers & Federica Marelli & Helle F. Jørgensen & W. Edward Visser & Carla Moran & Stefan Groeneweg & Carolina Avalos & Sean J. Jurgens & Nichola Figg & Alison Finigan & Neha Wali & Maura Ag, 2023. "Selenoprotein deficiency disorder predisposes to aortic aneurysm formation," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    16. Harry D Green & Alistair Jones & Jonathan P Evans & Andrew R Wood & Robin N Beaumont & Jessica Tyrrell & Timothy M Frayling & Christopher Smith & Michael N Weedon, 2021. "A genome-wide association study identifies 5 loci associated with frozen shoulder and implicates diabetes as a causal risk factor," PLOS Genetics, Public Library of Science, vol. 17(6), pages 1-13, June.
    17. Zhen Qiao & Julia Sidorenko & Joana A. Revez & Angli Xue & Xueling Lu & Katri Pärna & Harold Snieder & Peter M. Visscher & Naomi R. Wray & Loic Yengo, 2023. "Estimation and implications of the genetic architecture of fasting and non-fasting blood glucose," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    18. Xiaoyi Raymond Gao & Marion Chiariglione & Alexander J. Arch, 2022. "Whole-exome sequencing study identifies rare variants and genes associated with intraocular pressure and glaucoma," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    19. Romain Fournier & Zoi Tsangalidou & David Reich & Pier Francesco Palamara, 2023. "Haplotype-based inference of recent effective population size in modern and ancient DNA samples," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    20. Nicole Deflaux & Margaret Sunitha Selvaraj & Henry Robert Condon & Kelsey Mayo & Sara Haidermota & Melissa A. Basford & Chris Lunt & Anthony A. Philippakis & Dan M. Roden & Joshua C. Denny & Anjene Mu, 2023. "Demonstrating paths for unlocking the value of cloud genomics through cross cohort analysis," Nature Communications, Nature, vol. 14(1), pages 1-10, 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:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31625-5. 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: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    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.