TY - JOUR
T1 - The perception of quinine taste intensity is associated with common genetic variants in a bitter receptor cluster on chromosome 12
AU - Reed, Danielle R.
AU - Zhu, Gu
AU - Breslin, Paul A.S.
AU - Duke, Fujiko F.
AU - Henders, Anjali K.
AU - Campbell, Megan J.
AU - Montgomery, Grant W.
AU - Medland, Sarah E.
AU - Martin, Nicholas G.
AU - Wright, Margaret J.
N1 - Funding Information:
This work was supported by the National Health and Medical Research Council (241944, 219178, 389875 to N.G.M.), the Australian Research Council (DP0212016, DP0664638 to N.G.M. and M.J.W.) and the National Institutes of Health (DC004698 to D.R.R., DC02995 to P.A.S.B.). S.E.M. is supported by the National Health and Medical Research Council Fellowship Scheme. Funding to pay the Open Access Charge was provided by institutional funds from the Monell Chemical Senses Center.
PY - 2010/7/30
Y1 - 2010/7/30
N2 - The perceived taste intensities of quinine HCl, caffeine, sucrose octaacetate (SOA) and propylthiouracil (PROP) solutions were examined in 1457 twins and their siblings. Previous heritability modeling of these bitter stimuli indicated a common genetic factor for quinine, caffeine and SOA (22-28%), as well as separate specific genetic factors for PROP (72%) and quinine (15%). To identify the genes involved, we performed a genome-wide association study with the same sample as the modeling analysis, genotyped for approximately 610 000 single-nucleotide polymorphisms (SNPs). For caffeine and SOA, no SNP association reached a genome-wide statistical criterion. For PROP, the peak association was within TAS2R38 (rs713598, A49P, P = 1.6 × 10-104), which accounted for 45.9% of the trait variance. For quinine, the peak association was centered in a region that contains bitter receptor as well as salivary protein genes and explained 5.8% of the trait variance (TAS2R19, rs10772420, R299C, P = 1.8 × 10-15). We confirmed this association in a replication sample of twins of similar ancestry (P = 0.00001). The specific genetic factor for the perceived intensity of PROP was identified as the gene previously implicated in this trait (TAS2R38). For quinine, one or more bitter receptor or salivary proline-rich protein genes on chromosome 12 have alleles which affect its perception but tight linkage among very similar genes precludes the identification of a single causal genetic variant.
AB - The perceived taste intensities of quinine HCl, caffeine, sucrose octaacetate (SOA) and propylthiouracil (PROP) solutions were examined in 1457 twins and their siblings. Previous heritability modeling of these bitter stimuli indicated a common genetic factor for quinine, caffeine and SOA (22-28%), as well as separate specific genetic factors for PROP (72%) and quinine (15%). To identify the genes involved, we performed a genome-wide association study with the same sample as the modeling analysis, genotyped for approximately 610 000 single-nucleotide polymorphisms (SNPs). For caffeine and SOA, no SNP association reached a genome-wide statistical criterion. For PROP, the peak association was within TAS2R38 (rs713598, A49P, P = 1.6 × 10-104), which accounted for 45.9% of the trait variance. For quinine, the peak association was centered in a region that contains bitter receptor as well as salivary protein genes and explained 5.8% of the trait variance (TAS2R19, rs10772420, R299C, P = 1.8 × 10-15). We confirmed this association in a replication sample of twins of similar ancestry (P = 0.00001). The specific genetic factor for the perceived intensity of PROP was identified as the gene previously implicated in this trait (TAS2R38). For quinine, one or more bitter receptor or salivary proline-rich protein genes on chromosome 12 have alleles which affect its perception but tight linkage among very similar genes precludes the identification of a single causal genetic variant.
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U2 - 10.1093/hmg/ddq324
DO - 10.1093/hmg/ddq324
M3 - Article
C2 - 20675712
AN - SCOPUS:77957883532
VL - 19
SP - 4278
EP - 4285
JO - Human Molecular Genetics
JF - Human Molecular Genetics
SN - 0964-6906
IS - 21
M1 - ddq324
ER -