Liang-Dar Hwang

Genetic Analysis of Chemosensory Traits in Human Twins

We explored genetic influences on the perception of taste and smell stimuli. Adult twins rated the chemosensory aspects of water, sucrose, sodium chloride, citric acid, ethanol, quinine hydrochloride, phenylthiocarbamide (PTC), potassium chloride, calcium chloride, cinnamon, androstenone, Galaxolide™, cilantro, and basil. For most traits, individual differences were stable over time and some traits were heritable (h(2) from 0.41 to 0.71). Subjects were genotyped for 44 single nucleotide polymorphisms within and near genes related to taste and smell. The results of these association analyses confirmed previous genotype-phenotype results for PTC, quinine, and androstenone. New associations were detected for ratings of basil and a bitter taste receptor gene, TAS2R60, and between cilantro and variants in three genes (TRPA1, GNAT3, and TAS2R50). The flavor of ethanol was related to variation within an olfactory receptor gene (OR7D4) and a gene encoding a subunit of the epithelial sodium channel (SCNN1D). Our study demonstrates that person-to-person differences in the taste and smell perception of simple foods and drinks are partially accounted for by genetic variation within chemosensory pathways.

Preferences for Salty and Sweet Tastes Are Elevated and Related to Each Other during Childhood

Background The present study aimed to determine if salty and sweet taste preferences in children are related to each other, to markers of growth, and to genetic differences. Methods We conducted a 2-day, single-blind experimental study using the Monell two-series, forced-choice, paired-comparison tracking method to determine taste preferences. The volunteer sample consisted of a racially/ethnically diverse group of children, 5–10 years of age (n = 108), and their mothers (n = 83). After excluding those mothers who did not meet eligibility and children who did not understand or comply with study procedures, the final sample was 101 children and 76 adults. The main outcome measures were most preferred concentration of salt in broth and crackers; most preferred concentration of sucrose in water and jelly; reported dietary intake of salty and sweet foods; levels of a bone growth marker; anthropometric measurements such as height, weight, and percent body fat; and TAS1R3 (sweet taste receptor) genotype. Results Children preferred higher concentrations of salt in broth and sucrose in water than did adults, and for both groups, salty and sweet taste preferences were significantly and positively correlated. In children, preference measures were related to reported intake of sodium but not of added sugars. Children who were tall for their age preferred sweeter solutions than did those that were shorter and percent body fat was correlated with salt preference. In mothers but not in children, sweet preference correlated with TAS1R3 genotype. Conclusions and Relevance For children, sweet and salty taste preferences were positively correlated and related to some aspects of real-world food intake. Complying with recommendations to reduce added sugars and salt may be more difficult for some children, which emphasizes the need for new strategies to improve childrens diets.

Sweet Taste Perception is Associated with Body Mass Index at the Phenotypic and Genotypic Level

Investigations on the relationship between sweet taste perception and body mass index (BMI) have been inconclusive. Here, we report a longitudinal analysis using a genetically informative sample of 1,576 adolescent Australian twins to explore the relationship between BMI and sweet taste. First, we estimated the phenotypic correlations between perception scores for four different sweet compounds (glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame) and BMI. Then, we computed the association between adolescent taste perception and BMI in early adulthood (reported 9 years later). Finally, we used twin modeling and polygenic risk prediction analysis to investigate the genetic overlap between BMI and sweet taste perception. Our findings revealed that BMI in early adulthood was significantly associated with each of the sweet perception scores, with the strongest correlation observed in aspartame with r = 0.09 (p = .007). However, only limited evidence of association was observed between sweet taste perception and BMI that was measured at the same time (in adolescence), with the strongest evidence of association observed for glucose with a correlation coefficient of r = 0.06 (p = .029) and for aspartame with r = 0.06 (p = .035). We found a significant (p < .05) genetic correlation between glucose and NHDC perception and BMI. Our analyses suggest that sweet taste perception in adolescence can be a potential indicator of BMI in early adulthood. This association is further supported by evidence of genetic overlap between the traits, suggesting that some BMI genes may be acting through biological pathways of taste perception.

Caffeine bitterness is related to daily caffeine intake and bitter receptor mRNA abundance in human taste tissue

We investigated whether the abundance of bitter receptor mRNA expression from human taste papillae is related to an individual’s perceptual ratings of bitter intensity and habitual intake of bitter drinks. Ratings of the bitterness of caffeine and quinine and three other bitter stimuli (urea, propylthiouracil, and denatonium benzoate) were compared with relative taste papilla mRNA abundance of bitter receptors that respond to the corresponding bitter stimuli in cell-based assays (TAS2R4, TAS2R10, TAS2R38, TAS2R43, and TAS2R46). We calculated caffeine and quinine intake from a food frequency questionnaire. The bitterness of caffeine was related to the abundance of the combined mRNA expression of these known receptors, r = 0.47, p = .05, and self-reported daily caffeine intake, t(18) = 2.78, p = .012. The results of linear modeling indicated that 47% of the variance among subjects in the rating of caffeine bitterness was accounted for by these two factors (habitual caffeine intake and taste receptor mRNA abundance). We observed no such relationships for quinine but consumption of its primary dietary form (tonic water) was uncommon. Overall, diet and TAS2R gene expression in taste papillae are related to individual differences in caffeine perception.

Assessment of moderate coffee consumption and risk of epithelial ovarian cancer: a Mendelian randomization study

Background Coffee consumption has been shown to be associated with various health outcomes in observational studies. However, evidence for its association with epithelial ovarian cancer (EOC) is inconsistent and it is unclear whether these associations are causal. Methods We used single nucleotide polymorphisms associated with (i) coffee and (ii) caffeine consumption to perform Mendelian randomization (MR) on EOC risk. We conducted a two-sample MR using genetic data on 44 062 individuals of European ancestry from the Ovarian Cancer Association Consortium (OCAC), and combined instrumental variable estimates using a Wald-type ratio estimator. Results For all EOC cases, the causal odds ratio (COR) for genetically predicted consumption of one additional cup of coffee per day was 0.92 [95% confidence interval (CI): 0.79, 1.06]. The COR was 0.90 (95% CI: 0.73, 1.10) for high-grade serous EOC. The COR for genetically predicted consumption of an additional 80 mg caffeine was 1.01 (95% CI: 0.92, 1.11) for all EOC cases and 0.90 (95% CI: 0.73, 1.10) for high-grade serous cases. Conclusions We found no evidence indicative of a strong association between EOC risk and genetically predicted coffee or caffeine levels. However, our estimates were not statistically inconsistent with earlier observational studies and we were unable to rule out small protective associations.

Cross Sectional Association between Spatially Measured Walking Bouts and Neighborhood Walkability.

Walking is the most popular choice of aerobic physical activity to improve health among U.S. adults. Physical characteristics of the home neighborhood can facilitate or hinder walking. The purpose of this study was to quantify neighborhood walking, using objective methods and to examine the association between counts of walking bouts in the home neighborhood and neighborhood walkability. This was a cross-sectional study of 106 adults who wore accelerometers and GPS devices for two weeks. Walking was quantified within 1, 2, and 3 km Euclidean (straight-line) and network buffers around the geocoded home location. Walkability was estimated using a commercially available index. Walking bout counts increased with buffer size and were associated with walkability, regardless of buffer type or size (p < 0.001). Quantification of walking bouts within (and outside) of pre-defined neighborhood buffers of different sizes and types allowed for the specification of walking locations to better describe and elucidate walking behaviors. These data support the concept that neighborhood characteristics can influence walking among adults.

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

BackgroundHuman perception of bitter substances is partially genetically determined. Previously we discovered a single nucleotide polymorphism (SNP) within the cluster of bitter taste receptor genes 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.ResultsWe 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.ConclusionsThese 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.

Genetic analysis of impaired trimethylamine metabolism using whole exome sequencing

BackgroundTrimethylaminuria (TMAU) is a genetic disorder whereby people cannot convert trimethylamine (TMA) to its oxidized form (TMAO), a process that requires the liver enzyme FMO3. Loss-of-function variants in the FMO3 gene are a known cause of TMAU. In addition to the inability to metabolize TMA precursors like choline, patients often emit a characteristic odor because while TMAO is odorless, TMA has a fishy smell. The Monell Chemical Senses Center is a research institute with a program to evaluate people with odor complaints for TMAU.MethodsHere we evaluated ten subjects by (1) odor evaluation by a trained sensory panel, (2) analysis of their urine concentration of TMA relative to TMAO before and after choline ingestion, and (3) whole exome sequencing as well as subsequent variant analysis of all ten samples to investigate the genetics of TMAU.ResultsWhile all subjects reported they often emitted a fish-like odor, none had this malodor during sensory evaluation. However, all were impaired in their ability to produce >90% TMAO/TMA in their urine and thus met the criteria for TMAU. To probe for genetic causes, the exome of each subject was sequenced, and variants were filtered by genes with a known (FMO3) or expected effect on TMA metabolism function (other oxidoreductases). We filtered the remaining variants by allele frequency and predicated functional effects. We identified one subject that had a rare loss-of-function FMO3 variant and six with more common decreased-function variants. In other oxidoreductases genes, five subjects had four novel rare single-nucleotide polymorphisms as well as one rare insertion/deletion. Novel in this context means no investigators have previously linked these variants to TMAU although they are in dbSNP.ConclusionsThus, variants in genes other than FMO3 may cause TMAU and the genetic variants identified here serve as a starting point for future studies of impaired TMA metabolism.