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Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste

Liang-Dar Hwang, Puya Gharahkhani, Paul A. S. Breslin, Scott D. Gordon, Gu Zhu, Nicholas G. Martin, Nicholas G. Martin, Danielle R. Reed, Margaret J. Wright
doi: https://doi.org/10.1101/296269
Liang-Dar Hwang
1QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia
2Queensland Brain Institute, University of Queensland, St Lucia, Queensland 4072, Australia
3Faculty of Medicine, University of Queensland, Herston, Queensland 4006, Australia
4University of Queensland Diamantina Institute, University of Queensland, Translational Research Institute, Woolloongabba, Queensland 4102, Australia
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Puya Gharahkhani
1QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia
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Paul A. S. Breslin
5Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA
6Department of Nutritional Sciences, School of Environmental and Biological Sciences, Rutgers University, New Brunswick NJ, 08901 USA
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Scott D. Gordon
1QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia
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Gu Zhu
1QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia
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Nicholas G. Martin
1QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia
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Nicholas G. Martin
1QIMR Berghofer Medical Research Institute, Herston, Queensland 4006, Australia
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Danielle R. Reed
5Monell Chemical Senses Center, Philadelphia, Pennsylvania 19104, USA
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Margaret J. Wright
2Queensland Brain Institute, University of Queensland, St Lucia, Queensland 4072, Australia
7Centre for Advanced Imaging, University of Queensland, St Lucia, Queensland 4072, Australia
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Abstract

Human perception of bitter substances is partially genetically determined. Previously we discovered a single nucleotide polymorphism (SNP) within the bitter taste receptor gene TAS2R19 on chromosome 12 that accounts for 5.8% of the variance in the perceived intensity rating of quinine, and we strengthened the classic association between TAS2R38 genotype and the bitterness of propylthiouracil (PROP). Here we performed a genome-wide association study (GWAS) using a 40% larger sample (n = 1999) together with a bivariate approach to detect previously unidentified common variants with small effects on bitter perception. We identified two signals, both with small effects (< 2%), within the bitter taste receptor clusters on chromosomes 7 and 12, which influence the perceived bitterness of denatonium benzoate and sucrose octaacetate respectively. We also provided the first independent replication for an association of caffeine bitterness on chromosome 12. Furthermore, we provided evidence for pleiotropic effects on quinine, caffeine, sucrose octaacetate and denatonium benzoate for the three SNPs on chromosome 12 and the functional importance of the SNPs for denatonium benzoate bitterness. These findings provide new insights into the genetic architecture of bitter taste and offer a useful starting point for determining the biological pathways linking perception of bitter substances.

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Posted April 06, 2018.
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Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste
Liang-Dar Hwang, Puya Gharahkhani, Paul A. S. Breslin, Scott D. Gordon, Gu Zhu, Nicholas G. Martin, Nicholas G. Martin, Danielle R. Reed, Margaret J. Wright
bioRxiv 296269; doi: https://doi.org/10.1101/296269
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Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste
Liang-Dar Hwang, Puya Gharahkhani, Paul A. S. Breslin, Scott D. Gordon, Gu Zhu, Nicholas G. Martin, Nicholas G. Martin, Danielle R. Reed, Margaret J. Wright
bioRxiv 296269; doi: https://doi.org/10.1101/296269

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