Table lists the sample sizes, age, sex and other details for the discovery and replication subject populations.
Discovery and replication sample characteristics
For caffeine and SOA, no single-nucleotide polymorphisms (SNPs) reached our genome-wide significance threshold of 1.136 × 10−8
(see reference 12
for rationale for threshold; Fig. ). Previous research has demonstrated that a person's thresholds or perceived intensity ratings for caffeine, SOA and quinine are correlated (4
), suggesting that these individual differences arise from a common mechanism. However, we found no overlapping genetic associations for all three taste stimuli. For the PROP solution, 157 SNPs (30 of which were genotyped) reached this criterion P
-value, with TAS2R38
on chromosome 7 at the epicenter. The strongest signals in this region were observed at rs713598
= 1.6 × 10−104
) and rs10246939
= 1.1 × 10−101
). This region accounted for a maximum trait variance of 45.9%. When this association was accounted for (i.e. after conditioning on the genotyped peak SNP, rs10246939
), there was little evidence for a nearby secondary peak (chromosome 7: rs13238628, P
= 2.1 × 10−6.
). The two highest secondary peaks identified after conditioning on the peak SNP may be due to chance (chromosome 2: rs4141835
= 6.8 × 10−7
; chromosome 7: rs4727180
= 2.1 × 10−6
). The results for PROP-saturated paper overlapped with those for the solution, and all SNPs were within or near TAS2R38
= 2.10 × 10−42
). A region near a previously identified modifier locus (chromosome 5; TAS2R1
) approached but did not meet the statistical criterion for genome-wide significance (rs6867567
= 2.20 × 10−7
). For other details, see Supplementary Material, Table S1
Figure 1. Genome-wide association for PROP perception (A and B), followed by regional association between 7q34 variants and PROP perception (C) and LD among markers for the 7q34 region (D). (A) and (B) The observed –log 10 P-values by position (Mbp) for (more ...)
For quinine, 19 SNPs (12 of which were genotyped) from chromosome 12, near and within a cluster of bitter receptor and two salivary protein genes, were associated with bitterness perception. Eleven of the associated markers were within the introns of two proline-rich protein genes, and the other SNP coded for an arginine-to-cysteine substitution at amino acid 299 (R299C) in the bitter receptor TAS2R19 (rs10772420, R299C, P = 1.8 × 10−15; formerly known as TAS2R48) (Fig. ). This region accounted for a maximum trait variance of 5.77%. After conditioning on the peak SNP (rs10772420), no secondary peaks reached the statistical criterion for genome-wide significance. We tested this association for quinine in an independent group of twins from the general population, collected as a part of a larger study on the genetics of taste perception conducted at a festival held in Twinsburg, OH, USA. One SNP (rs10772420) was genotyped, chosen from a subset of markers from the discovery sample because it was tightly associated with the ratings of quinine intensity and because it created an amino acid change in a bitter receptor (TaqMan, Applied Biosystems). The results indicated that the A allele of the genetic variant TAS2R19 R299C (rs10772420) was associated with more intense quinine perception [F(2,66) = 13.8, P = 0.00001] with the same direction of effect and the same allele associated with increased quinine sensitivity in both the discovery and replication samples (Fig. ).
Genome-wide association for quinine perception (A), followed by regional association between 12p13.2 variants and quinine perception (B) and LD among markers for the 12p13.2 region (C). See Figure for details.
Figure 3. Average bitter taste intensity of quinine as rated by people from the discovery (top) and replication (bottom) samples grouped by their rs10772420 genotype. LMS, labeled magnitude scale; VAS, visual analogue scale. Values are means and confidence intervals (more ...)