ORCID Profile
0000-0002-5535-2199
Current Organisation
University of Queensland
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Statistical and quantitative genetics | Applied statistics | Sensory systems | Statistics
Publisher: Elsevier BV
Date: 05-2020
Publisher: eLife Sciences Publications, Ltd
Date: 06-07-2022
Publisher: Oxford University Press (OUP)
Date: 13-09-2012
Publisher: Springer Science and Business Media LLC
Date: 17-09-2018
Publisher: MDPI AG
Date: 08-04-2016
Publisher: Springer Science and Business Media LLC
Date: 13-02-2021
Publisher: Cambridge University Press (CUP)
Date: 17-07-2015
DOI: 10.1017/THG.2015.42
Abstract: The perception of sweetness varies among in iduals but the sources of this variation are not fully understood. Here, in a s le of 1,901 adolescent and young adults (53.8% female 243 MZ and 452 DZ twin pairs, 511 unpaired in iduals mean age 16.2 ± 2.8, range 12–26 years), we studied the variation in the perception of sweetness intensity of two monosaccharides and two high-potency sweeteners: glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame. Perceived intensity for all sweeteners decreased with age (2–5% per year) and increased with the history of otitis media (6–9%). Males rated aspartame slightly stronger than females (7%). We found similar heritabilities for sugars (glucose: h 2 = 0.31, fructose: h 2 = 0.34) and high-potency sweeteners (NHDC: h 2 = 0.31, aspartame: h 2 = 0.30) all were in the modest range. Multivariate modeling showed that a common genetic factor accounted for % of the genetic variance in the four sweeteners, suggesting that in idual differences in perceived sweet intensity, which are partly due to genetic factors, may be attributed to a single set of genes. This study provided evidence of the shared genetic pathways between the perception of sugars and high-potency sweeteners.
Publisher: Public Library of Science (PLoS)
Date: 17-03-2014
Publisher: Springer Science and Business Media LLC
Date: 15-11-2018
DOI: 10.1038/S41598-018-34713-Z
Abstract: Consumption of coffee, tea and alcohol might be shaped by in idual differences in bitter taste perception but inconsistent observational findings provide little insight regarding causality. We conducted Mendelian randomization analyses using genetic variants associated with the perception of bitter substances (rs1726866 for propylthiouracil [PROP], rs10772420 for quinine and rs2597979 for caffeine) to evaluate the intake of coffee, tea and alcohol among up to 438,870 UK Biobank participants. A standard deviation (SD) higher in genetically predicted bitterness of caffeine was associated with increased coffee intake (0.146 [95%CI: 0.103, 0.189] cups/day), whereas a SD higher in those of PROP and quinine was associated with decreased coffee intake (−0.021 [−0.031, −0.011] and −0.081 [−0.108, −0.054] cups/day respectively). Higher caffeine perception was also associated with increased risk of being a heavy ( cups/day) coffee drinker (OR 1.207 [1.126, 1.294]). Opposite pattern of associations was observed for tea possibly due to the inverse relationship between both beverages. Alcohol intake was only negatively associated with PROP perception (−0.141 [−1.88, −0.94] times/month per SD increase in PROP bitterness). Our results reveal that bitter perception is causally associated with intake of coffee, tea and alcohol, suggesting a role of bitter taste in the development of bitter beverage consumption.
Publisher: Cold Spring Harbor Laboratory
Date: 31-08-2021
DOI: 10.1101/2021.08.28.21262763
Abstract: Sudden smell loss is a specific early symptom of COVID-19, with an estimated prevalence of ~40% to 75%. Smell impairment affects physical and mental health, and dietary behavior. Thus, it is critical to understand the rate and time course of smell recovery. To characterize smell function and recovery up to 11 months post COVID-19 infection. This longitudinal survey of in iduals suffering COVID-19-related smell loss assessed disease symptoms and gustatory and olfactory function. Participants (n=12,313) who completed an initial respiratory symptoms, chemosensory function and COVID-19 diagnosis survey (S1) between April and September 2020 and completed a follow-up survey (S2) between September 2020 and February 2021 27.5% participants responded (n=3,386), with 1,468 being diagnosed with COVID-19 and suffering co-occurring smell and taste loss at the beginning of their illness. Primary outcomes are ratings of smell and taste function on a visual analog scale, and self-report of parosmia (smell distortions) and phantosmia (unexplained smells). Secondary outcomes include a checklist of other COVID-19 symptoms. On follow-up (median time since COVID-19 onset ~200 days), ~60% of women and ~48% of men reported less than 80% of their pre-illness smell ability. Taste typically recovered faster than smell, and taste loss rarely persisted if smell recovered. Prevalence of parosmia and phantosmia was ~10% of participants in S1 and increased substantially in S2: ~47% for parosmia and ~25% for phantosmia. Persistent smell impairment was associated with more symptoms overall, suggesting it may be a key marker of long-COVID. During COVID-19 illness, the ability to smell was slightly lower among those who did not recover their pre-illness ability to smell at S2. While smell loss improves for many in iduals who lost it due to COVID-19, the prevalence of parosmia and phantosmia increases substantially over time. Olfactory dysfunction is also associated with wider COVID-19 symptoms and may persist for many months after COVID-19 onset. Taste loss in the absence of smell loss is rare. Persistent qualitative smell symptoms are emerging as common long term sequelae more research into treatment options is strongly warranted given that conservative estimates suggest millions of in iduals may experience parosmia following COVID-19. Healthcare providers worldwide need to be prepared to treat post COVID-19 secondary effects on physical and mental health. This project was pre-registered at OSF: osf.io/3e6zc . What are the characteristics of smell and taste recovery of COVID-19 patients? In this preregistered observational study of 1,468 participants, smell loss is associated with a higher number of COVID-19 symptoms, and may persist for at least 11 months following disease onset. While a majority of participants report quantitative improvement in their ability to smell, the prevalence of parosmia and phantosmia increases substantially at follow-up. Taste recovers faster than smell, suggesting taste and smell recover separately and can be distinguished by the respondents. Olfactory dysfunction appears to be a component of long-COVID, with parosmia as a prominent symptom in almost half of those with smell loss. More research into treatment is needed, especially given that olfactory dysfunction is associated with depression and loss of appetite. Health professionals should be aware of these common and long lasting effects.
Publisher: Cold Spring Harbor Laboratory
Date: 11-01-2019
DOI: 10.1101/518027
Abstract: Genome-wide association studies (GWAS) are an important method for mapping genetic variation underlying complex traits and diseases. Tools to visualize, annotate and analyse results from these studies can be used to generate hypotheses about the molecular mechanisms underlying the associations. The Complex-Traits Genetics Virtual Lab (CTG-VL) integrates over a thousand publicly-available GWAS summary statistics, a suite of analysis tools, visualization functions and erse data sets for genomic annotations. CTG-VL also makes available results from gene, pathway and tissue-based analyses from over 1,500 complex-traits allowing to assess pleiotropy not only at the genetic variant level but also at the gene, pathway and tissue levels. In this manuscript, we showcase the platform by analysing GWAS summary statistics of mood swings derived from UK Biobank. Using analysis tools in CTG-VL we highlight hippoc us as a potential tissue involved in mood swings, and that pathways including neuron apoptotic process may underlie the genetic associations. Further, we report a negative genetic correlation with educational attainment rG = −0.41 ± 0.018 and a potential causal effect of BMI on mood swings OR = 1.01 (95% CI = 1.00–1.02). Using CTG-VL’s database, we show that pathways and tissues associated with mood swings are also associated with neurological traits including reaction time and neuroticism, as well as traits such age at menopause and age at first live birth. CTG-VL is a platform with the most complete set of tools to carry out post-GWAS analyses. The CTG-VL is freely available at genoma.io as an online web application.
Publisher: Cambridge University Press (CUP)
Date: 04-12-2020
DOI: 10.1017/S2040174420001105
Abstract: Recent studies have used Mendelian randomization (MR) to investigate the observational association between low birth weight (BW) and increased risk of cardiometabolic outcomes, specifically cardiovascular disease, glycemic traits, and type 2 diabetes (T2D), and inform on the validity of the Barker hypothesis. We used simulations to assess the validity of these previous MR studies, and to determine whether a better formulated model can be used in this context. Genetic and phenotypic data were simulated under a model of no direct causal effect of offspring BW on cardiometabolic outcomes and no effect of maternal genotype on offspring cardiometabolic risk through intrauterine mechanisms where the observational relationship between BW and cardiometabolic risk was driven entirely by horizontal genetic pleiotropy in the offspring (i.e. offspring genetic variants affecting both BW and cardiometabolic disease simultaneously rather than a mechanism consistent with the Barker hypothesis). We investigated the performance of four commonly used MR analysis methods (weighted allele score MR (WAS-MR), inverse variance weighted MR (IVW-MR), weighted median MR (WM-MR), and MR-Egger) and a new approach, which tests the association between maternal genotypes related to offspring BW and offspring cardiometabolic risk after conditioning on offspring genotype at the same loci. We caution against using traditional MR analyses, which do not take into account the relationship between maternal and offspring genotypes, to assess the validity of the Barker hypothesis, as results are biased in favor of a causal relationship. In contrast, we recommend the aforementioned conditional analysis framework utilizing maternal and offspring genotypes as a valid test of not only the Barker hypothesis, but also to investigate hypotheses relating to the Developmental Origins of Health and Disease more broadly.
Publisher: Cold Spring Harbor Laboratory
Date: 26-07-2020
DOI: 10.1101/2020.07.22.20157263
Abstract: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. This preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in in iduals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+ n=4148) or negative (C19- n=546) COVID-19 laboratory test outcome. Logistic regression models identified singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19-groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both single and cumulative feature models (ROC AUC=0.72), with additional features providing negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ∼50% of participants and was best predicted by time since illness onset. As smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 OR ), which can be deployed when viral lab tests are impractical or unavailable.
Publisher: Cold Spring Harbor Laboratory
Date: 24-08-2023
DOI: 10.1101/2023.08.22.23294446
Abstract: Perinatal traits are influenced by genetic variants from both fetal and maternal genomes. Genome-wide association studies (GWAS) of these phenotypes have typically involved separate fetal and maternal scans, however, this approach may be inefficient as it does not utilize the information shared across the in idual GWAS. In this manuscript we investigate the performance of three strategies to detect loci in maternal and fetal GWAS of the same trait: (i) the traditional strategy of analysing maternal and fetal GWAS separately (ii) a novel two degree of freedom test which combines information from maternal and fetal GWAS and (iii) a novel one degree of freedom test where signals from maternal and fetal GWAS are meta-analysed together conditional on the estimated s le overlap. We demonstrate through a combination of analytical formulae and data simulation that the optimal strategy depends on the extent of s le overlap/relatedness between the maternal and fetal GWAS, the correlation between own and offspring phenotypes, whether loci jointly exhibit fetal and maternal effects, and if so, whether these effects are directionally concordant. We apply our methods to summary results statistics from a recent GWAS meta-analysis of birth weight from deCODE, the UK Biobank and the Early Growth Genetics (EGG) consortium. Both the two degree of freedom (213 loci) and meta-analytic approach (226 loci) dramatically increase the number of robustly associated genetic loci for birth weight relative to separately analysing the scans (183 loci). Our best strategy identifies an additional 62 novel loci compared to the most recent published meta-analysis of birth weight and implicates both known and new biological pathways in the aetiology of the trait. We implement our methods in the online DINGO ( D irect and IN direct effects analysis of G enetic l O ci) software package, which allows users to perform one and/or two degree of freedom tests easily and computationally efficiently across the genome. We conclude that whilst the novel two degree of freedom test may be particularly useful for the analysis of certain perinatal phenotypes where many loci exhibit discordant maternal and fetal genetic effects, for most phenotypes, a simple meta-analytic strategy is likely to perform best, particularly in situations where maternal and fetal GWAS only partially overlap.
Publisher: Public Library of Science (PLoS)
Date: 26-10-2020
DOI: 10.1371/JOURNAL.PGEN.1009154
Abstract: Indirect parental genetic effects may be defined as the influence of parental genotypes on offspring phenotypes over and above that which results from the transmission of genes from parents to their children. However, given the relative paucity of large-scale family-based cohorts around the world, it is difficult to demonstrate parental genetic effects on human traits, particularly at in idual loci. In this manuscript, we illustrate how parental genetic effects on offspring phenotypes, including late onset conditions, can be estimated at in idual loci in principle using large-scale genome-wide association study (GWAS) data, even in the absence of parental genotypes. Our strategy involves creating “virtual” mothers and fathers by estimating the genotypic dosages of parental genotypes using physically genotyped data from relative pairs. We then utilize the expected dosages of the parents, and the actual genotypes of the offspring relative pairs, to perform conditional genetic association analyses to obtain asymptotically unbiased estimates of maternal, paternal and offspring genetic effects. We apply our approach to 19066 sibling pairs from the UK Biobank and show that a polygenic score consisting of imputed parental educational attainment SNP dosages is strongly related to offspring educational attainment even after correcting for offspring genotype at the same loci. We develop a freely available web application that quantifies the power of our approach using closed form asymptotic solutions. We implement our methods in a user-friendly software package IMPISH ( IM puting P arental genotypes I n S iblings and H alf Siblings) which allows users to quickly and efficiently impute parental genotypes across the genome in large genome-wide datasets, and then use these estimated dosages in downstream linear mixed model association analyses. We conclude that imputing parental genotypes from relative pairs may provide a useful adjunct to existing large-scale genetic studies of parents and their offspring.
Publisher: Oxford University Press (OUP)
Date: 25-11-2017
DOI: 10.1093/IJE/DYX236
Publisher: Oxford University Press (OUP)
Date: 25-12-2020
Abstract: In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in in iduals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0–100 visual analog scales (VAS) for participants reporting a positive (C19+ n = 4148) or negative (C19− n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19− groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: −82.5 ± 27.2 points C19−: −59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying in iduals with a high likelihood of having COVID-19, we propose a novel 0–10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 & OR & 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2017
Publisher: Oxford University Press (OUP)
Date: 27-02-2019
DOI: 10.1093/IJE/DYZ019
Abstract: There is considerable interest in estimating the causal effect of a range of maternal environmental exposures on offspring health-related outcomes. Previous attempts to do this using Mendelian randomization methodologies have been h ered by the paucity of epidemiological cohorts with large numbers of genotyped mother–offspring pairs. We describe a new statistical model that we have created which can be used to estimate the effect of maternal genotypes on offspring outcomes conditional on offspring genotype, using both in idual-level and summary-results data, even when the extent of s le overlap is unknown. We describe how the estimates obtained from our method can subsequently be used in large-scale two-s le Mendelian randomization studies to investigate the causal effect of maternal environmental exposures on offspring outcomes. This includes studies that aim to assess the causal effect of in utero exposures related to fetal growth restriction on future risk of disease in offspring. We illustrate our framework using ex les related to offspring birthweight and cardiometabolic disease, although the general principles we espouse are relevant for many other offspring phenotypes. We advocate for the establishment of large-scale international genetics consortia that are focused on the identification of maternal genetic effects and committed to the public sharing of genome-wide summary-results data from such efforts. This information will facilitate the application of powerful two-s le Mendelian randomization studies of maternal exposures and offspring outcomes.
Publisher: Oxford University Press (OUP)
Date: 20-06-2020
Abstract: Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments, such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, and generally lacked quantitative measurements. Here, we report the development, implementation, and initial results of a multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, and 8 others, aged 19–79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste, and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change ±100) revealed a mean reduction of smell (−79.7 ± 28.7, mean ± standard deviation), taste (−69.0 ± 32.6), and chemesthetic (−37.3 ± 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell but also affects taste and chemesthesis. The multimodal impact of COVID-19 and the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.
Publisher: Elsevier BV
Date: 05-2019
Publisher: Springer Science and Business Media LLC
Date: 28-09-2020
Publisher: Oxford University Press (OUP)
Date: 09-08-2016
Publisher: Cold Spring Harbor Laboratory
Date: 02-03-2020
Publisher: Springer Science and Business Media LLC
Date: 14-09-2021
DOI: 10.1038/S41467-021-25723-Z
Abstract: Estimation of direct and indirect (i.e. parental and/or sibling) genetic effects on phenotypes is becoming increasingly important. We compare several multivariate methods that utilize summary results statistics from genome-wide association studies to determine how well they estimate direct and indirect genetic effects. Using data from the UK Biobank, we contrast point estimates and standard errors at in idual loci compared to those obtained using in idual level data. We show that Genomic structural equation modelling (SEM) outperforms the other methods in accurately estimating conditional genetic effects and their standard errors. We apply Genomic SEM to fertility data in the UK Biobank and partition the genetic effect into female and male fertility and a sibling specific effect. We identify a novel locus for fertility and genetic correlations between fertility and educational attainment, risk taking behaviour, autism and subjective well-being. We recommend Genomic SEM be used to partition genetic effects into direct and indirect components when using summary results from genome-wide association studies.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2020
DOI: 10.1038/S41598-020-60488-3
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: Springer Science and Business Media LLC
Date: 16-01-2021
Publisher: Wiley
Date: 13-10-2021
DOI: 10.1002/IJC.33308
Publisher: Oxford University Press (OUP)
Date: 05-2020
DOI: 10.1093/IJE/DYAA069
Publisher: Springer Science and Business Media LLC
Date: 03-10-2020
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1093/AJCN/NQZ043
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2022
DOI: 10.1161/HYPERTENSIONAHA.121.17701
Abstract: Observational epidemiological studies have reported that higher maternal blood pressure (BP) during pregnancy is associated with increased future risk of offspring cardiometabolic disease. However, it is unclear whether this association represents a causal relationship through intrauterine mechanisms. We used a Mendelian randomization (MR) framework to examine the relationship between unweighted maternal genetic scores for systolic BP and diastolic BP and a range of cardiometabolic risk factors in the offspring of up to 29 708 genotyped mother-offspring pairs from the UKB study (UK Biobank) and the HUNT study (Trøndelag Health). We conducted similar analyses in up to 21 423 father-offspring pairs from the same cohorts. We confirmed that the BP-associated genetic variants from the general population s le also had similar effects on maternal BP during pregnancy in independent cohorts. We did not detect any association between maternal (or paternal) unweighted genetic scores and cardiometabolic offspring outcomes in the meta-analysis of UKB and HUNT after adjusting for offspring genotypes at the same loci. We find little evidence to support the notion that maternal BP is a major causal risk factor for adverse offspring cardiometabolic outcomes in later life.
Publisher: Cambridge University Press (CUP)
Date: 04-2020
DOI: 10.1017/THG.2020.19
Abstract: This paper is about Nick’s contribution to the field of taste genetics, how I became involved and how a study on the genetic association between the perception of sweetness and bitterness ended up examining the influence of intelligence on taste perception.
Publisher: MDPI AG
Date: 24-09-2019
DOI: 10.3390/NU11102285
Abstract: In iduals undergoing treatment for cancer can experience changes in taste or smell that are often assumed to affect constructs related to food behavior, although this relationship is rarely measured directly. To ascertain the extent to which measured changes in taste and smell during and after cancer treatment affect food behavior, we conducted a scoping review and completed a comparative analysis for studies that met our criteria, which were: they directly measured cancer patients’ (a) psychophysical response to taste and/or olfactory stimuli, and (b) food behavior (including food enjoyment, food preference, dietary intake) in people affected by cancer. Eleven studies met these criteria and were included in the review. All 11 studies evaluated taste and five also measured smell. A comparative analysis exploring taste and food behavior shows that a reduced sweet taste function (decreased sensitivity) was associated with a reduced intake of a variety of different macro and micro nutrients, reduced appetite, and overall lower energy intake. One out of six studies that measured smell and food measured observed changes in olfactory function following cancer treatment. There were no significant relationships reported between olfactory measures and food behavior. Taste changes that arise from cancer treatment appear to have a direct effect on food behavior, although there is a need for more research using standardized measures and larger s le sizes. A better understanding of taste alterations and their implications for dietary intake and food enjoyment will support optimal nutritional health by identifying strategies to help patients eat well during and after cancer treatment.
Publisher: Cambridge University Press (CUP)
Date: 05-08-2016
DOI: 10.1017/THG.2016.60
Abstract: 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 s le 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.
Publisher: SAGE Publications
Date: 24-01-2017
Abstract: We investigated whether the abundance of bitter receptor mRNA expression from human taste papillae is related to an in idual’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 in idual differences in caffeine perception.
Publisher: eLife Sciences Publications, Ltd
Date: 13-07-2022
DOI: 10.7554/ELIFE.73671
Abstract: Maternal genetic effects can be defined as the effect of a mother’s genotype on the phenotype of her offspring, independent of the offspring’s genotype. Maternal genetic effects can act via the intrauterine environment during pregnancy and/or via the postnatal environment. In this manuscript, we present a simple extension to the basic adoption design that uses structural equation modelling (SEM) to partition maternal genetic effects into prenatal and postnatal effects. We examine the power, utility and type I error rate of our model using simulations and asymptotic power calculations. We apply our model to polygenic scores of educational attainment and birth weight associated variants, in up to 5,178 adopted singletons, 943 trios, 2687 mother-offspring pairs, 712 father-offspring pairs and 347,980 singletons from the UK Biobank. Our results show the expected pattern of maternal genetic effects on offspring birth weight, but unexpectedly large prenatal maternal genetic effects on offspring educational attainment. Sensitivity and simulation analyses suggest this result may be at least partially due to adopted in iduals in the UK Biobank being raised by their biological relatives. We show that accurate modelling of these sorts of cryptic relationships is sufficient to bring type I error rate under control and produce asymptotically unbiased estimates of prenatal and postnatal maternal genetic effects. We conclude that there would be considerable value in following up adopted in iduals in the UK Biobank to determine whether they were raised by their biological relatives, and if so, to precisely ascertain the nature of these relationships. These adopted in iduals could then be incorporated into informative statistical genetics models like the one described in our manuscript to further elucidate the genetic architecture of complex traits and diseases.
Publisher: Oxford University Press (OUP)
Date: 09-06-2022
DOI: 10.1093/IJE/DYAC121
Abstract: Coffee consumption has been associated with several adverse pregnancy outcomes, although data from randomized–controlled trials are lacking. We investigate whether there is a causal relationship between coffee consumption and miscarriage, stillbirth, birthweight, gestational age and pre-term birth using Mendelian randomization (MR). A two-s le MR study was performed using summary results data from a genome-wide association meta-analysis of coffee consumption (N = 91 462) from the Coffee and Caffeine Genetics Consortium. Outcomes included self-reported miscarriage (N = 49 996 cases and 174 109 controls from a large meta-analysis) the number of stillbirths [N = 60 453 from UK Biobank (UKBB)] gestational age and pre-term birth (N = 43 568 from the 23andMe, Inc cohort) and birthweight (N = 297 356 reporting own birthweight and N = 210 248 reporting offspring’s birthweight from UKBB and the Early Growth Genetics Consortium). Additionally, a one-s le genetic risk score (GRS) analysis of coffee consumption in UKBB women (N up to 194 196) and the Avon Longitudinal Study of Parents and Children (N up to 6845 mothers and 4510 children) and its relationship with offspring outcomes was performed. Both the two-s le MR and one-s le GRS analyses showed no change in risk of sporadic miscarriages, stillbirths, pre-term birth or effect on gestational age connected to coffee consumption. Although both analyses showed an association between increased coffee consumption and higher birthweight, the magnitude of the effect was inconsistent. Our results suggest that coffee consumption during pregnancy might not itself contribute to adverse outcomes such as stillbirth, sporadic miscarriages and pre-term birth or lower gestational age or birthweight of the offspring.
Publisher: Oxford University Press (OUP)
Date: 23-07-2019
DOI: 10.1093/IJE/DYZ160
Abstract: The intrauterine environment is critical for fetal growth and development. However, observational associations between maternal gestational lipid concentrations and offspring birth weight (BW) have been inconsistent and ascertaining causality is challenging. We used a novel two-s le Mendelian randomization (MR) approach to estimate the causal effect of maternal gestational high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride concentrations on offspring BW. Single nucleotide polymorphisms (SNPs) associated with serum HDL-C, LDL-C and triglyceride concentrations identified in the Global Lipids Genetics Consortium genome-wide association study meta-analysis (n = 188 577 European-ancestry in iduals s le 1) were selected as instrumental variables. The effects of these SNPs on offspring BW were estimated using a structural equation model in the UK Biobank and Early Growth Genetics consortium (n = 230 069 European-ancestry in iduals s le 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects. We found no evidence for a causal effect of maternal gestational HDL-C, LDL-C or triglyceride concentrations on offspring BW [standard deviation change in BW per standard deviation higher in HDL-C = −0.005 (95% confidence interval: −0.039, 0.029), LDL-C = 0.014 (−0.017, 0.045), and triglycerides = 0.014 (−0.025, 0.052)]. Our findings suggest that maternal gestational HDL-C, LDL-C and triglyceride concentrations play a limited role in determining offspring BW. However, we cannot comment on the impact of these and other lipid fractions on fetal development more generally. Our study illustrates the power and flexibility of two-s le MR in assessing the causal effect of maternal environmental exposures on offspring outcomes.
Start Date: 07-2024
End Date: 06-2027
Amount: $424,237.00
Funder: Australian Research Council
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