GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics

Human perception of bitterness displays pronounced interindividual variation. This phenotypic variation is mirrored by equally pronounced genetic variation in the family of bitter taste receptor genes. To better understand the effects of common genetic variations on human bitter taste perception, we conducted a genome-wide association study on a discovery panel of 504 subjects and a validation panel of 104 subjects from the general population of São Paulo in Brazil. Correction for general taste-sensitivity allowed us to identify a SNP in the cluster of bitter taste receptors on chr12 (10.88- 11.24 Mb, build 36.1) significantly associated (best SNP: rs2708377, P = 5.31 × 10−13, r2 = 8.9%, β = −0.12, s.e. = 0.016) with the perceived bitterness of caffeine. This association overlaps with—but is statistically distinct from—the previously identified SNP rs10772420 influencing the perception of quinine bitterness that falls in the same bitter taste cluster. We replicated this association to quinine perception (P = 4.97 × 10−37, r2 = 23.2%, β = 0.25, s.e. = 0.020) and additionally found the effect of this genetic locus to be concentration specific with a strong impact on the perception of low, but no impact on the perception of high concentrations of quinine. Our study, thus, furthers our understanding of the complex genetic architecture of bitter taste perceptio

Sensitivity of Genome-Wide-Association Signals to Phenotyping Strategy: The PROP-TAS2R38 Taste Association as a Benchmark

Natural genetic variation can have a pronounced influence on human taste perception, which in turn may influence food preference and dietary choice. Genome-wide association studies represent a powerful tool to understand this influence. To help optimize the design of future genome-wide-association studies on human taste perception we have used the well-known TAS2R38-PROP association as a tool to determine the relative power and efficiency of different phenotyping and data-analysis strategies. The results show that the choice of both data collection and data processing schemes can have a very substantial impact on the power to detect genotypic variation that affects chemosensory perception. Based on these results we provide practical guidelines for the design of future GWAS studies on chemosensory phenotypes. Moreover, in addition to the TAS2R38 gene past studies have implicated a number of other genetic loci to affect taste sensitivity to PROP and the related bitter compound PTC. None of these other locations showed genome-wide significant associations in our study. To facilitate further, target-gene driven, studies on PROP taste perception we provide the genome-wide list of p-values for all SNPs genotyped in the current study

Metabomatching.

<p>Each subfigure compares the <i>CoLaus</i> pseudo-spectrum (bottom half) with the NMR spectrum (top half) of the most likely candidate for the associated metabolite. (A) rs37369 vs. 3-aminoisobutyrate. (B) rs2147896 in <i>PYROXD2</i> vs. trimethylamine (C) rs8101881 in <i>SLC7A9</i> vs. lysine (D) rs281408 in <i>FUT2</i> vs. fucose.</p

Allelic heterogeneity at the <i>AGXT2</i> locus.

<p>Abbreviations: <i>P_C, P_T</i> – P-values, <i>x_C, x_T</i> – multivariate effect sizes, <i>R²</i> – explained variance of full model, <i>R²_diff</i> – additional explained variance of full model compared to best single SNP association, <i>model P</i> – probability of observing same or equal <i>R²_diff</i> increase with the same stepwise model selection for 2,500 permuted phenotypes.</p