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

Author

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  • 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
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    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. 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.
    4. 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.
    5. 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.
    6. 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.
    7. 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.
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