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Cis-regulated expression of non-conserved lincRNAs associates with cardiometabolic related traits

Journal of Human Genetics volume 67, pages 307–310 (2022)Cite this article

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Abstract

Many complex disease risk loci map to intergenic regions containing long intergenic noncoding RNAs (lincRNAs). The majority of these is not conserved outside humans, raising the question whether genetically regulated expression of non-conserved and conserved lincRNAs has similar rates of association with complex traits. Here we leveraged data from the Genotype-Tissue Expression (GTEx) project and multiple public genome-wide association study (GWAS) resources. Using an established transcriptome-wide association study (TWAS) tool, FUSION, we interrogated the associations between cis-regulated expression of lincRNAs and multiple cardiometabolic traits. We found that cis-regulated expression of non-conserved lincRNAs had a strikingly similar trend of association with complex cardiometabolic traits as conserved lincRNAs. This finding challenges the conventional notion of conservation that has led to prioritization of conserved loci for functional studies and calls attention to the need to develop comprehensive strategies to study the large number of non-conserved human lincRNAs that may contribute to human disease.

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Fig. 1: Multivariable analysis.

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Acknowledgements

The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this paper were obtained from: dbGaP accession number phs000424.v8.p2 on 05/20/2020.

Funding

Support for this research was provided by grants from the National Institutes of Health (NIH) R01 GM127862 to ASF, and R01 HL132561, R01 HL113147, and K24 HL107643 to MPR.

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Author notes

  1. These authors contributed equally: Muredach P. Reilly, Andrea S. Foulkes.

Authors and Affiliations

  1. Biostatistics, Massachusetts General Hospital, Boston, MA, USA

    Tingyi Cao, Caitlin Selvaggi, Anjali Jha & Andrea S. Foulkes

  2. Department of Biostatistics, Harvard TH Chan School of Public Health, Boston, MA, USA

    Tingyi Cao & Anjali Jha

  3. Cardiology Division, Department of Medicine, Columbia University, New York, NY, USA

    Marcella E. O’Reilly, Esther Cynn, Heidi Lumish, Chenyi Xue & Muredach P. Reilly

  4. The Irving Institute for Clinical and Translational Sciences, Columbia University, New York, NY, USA

    Muredach P. Reilly

  5. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Andrea S. Foulkes

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  1. Tingyi Cao
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Correspondence to Tingyi Cao.

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Cao, T., O’Reilly, M.E., Selvaggi, C. et al. Cis-regulated expression of non-conserved lincRNAs associates with cardiometabolic related traits. J Hum Genet 67, 307–310 (2022). https://doi.org/10.1038/s10038-022-01012-5

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