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1.
Behav Genet ; 2021 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-33582897

RESUMO

The Classical Twin Method (CTM) compares the similarity of monozygotic (MZ) twins with that of dizygotic (DZ) twins to make inferences about the relative importance of genes and environment in the etiology of individual differences. The design has been applied to thousands of traits across the biomedical, behavioral and social sciences and is arguably the most widely used natural experiment known to science. The fundamental assumption of the CTM is that trait relevant environmental covariation within MZ pairs is the same as that found within DZ pairs, so that zygosity differences in within-pair variance must be due to genetic factors uncontaminated by the environment. This equal environments assumption (EEA) has been, and still is hotly contested, and has been mentioned as a possible contributing factor to the missing heritability conundrum. In this manuscript, we introduce a new model for testing the EEA, which we call the Augmented Classical Twin Design which uses identity by descent (IBD) sharing between DZ twin pairs to estimate separate environmental variance components for MZ and DZ twin pairs, and provides a test of whether these are equal. We show through simulation that given large samples of DZ twin pairs, the model provides unbiased estimates of variance components and valid tests of the EEA under strong assumptions (e.g. no epistatic variance, IBD sharing in DZ twins estimated accurately etc.) which may not hold in reality. Sample sizes in excess of 50,000 DZ twin pairs with genome-wide genetic data are likely to be required in order to detect substantial violations of the EEA with moderate power. Consequently, we recommend that the Augmented Classical Twin Design only be applied to datasets with very large numbers of DZ twin pairs (> 50,000 DZ twin pairs), and given the strong assumptions relating to the absence of epistatic variance, appropriate caution be exercised regarding interpretation of the results.

2.
Behav Genet ; 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33454873

RESUMO

Disaggregation and estimation of genetic effects from offspring and parents has long been of interest to statistical geneticists. Recently, technical and methodological advances have made the genome-wide and loci-specific estimation of direct offspring and parental genetic nurture effects more possible. However, unbiased estimation using these methods requires datasets where both parents and at least one child have been genotyped, which are relatively scarce. Our group has recently developed a method and accompanying software (IMPISH; Hwang et al. in PLoS Genet 16:e1009154, 2020) which is able to impute missing parental genotypes from observed data on sibships and estimate their effects on an offspring phenotype conditional on the effects of genetic transmission. However, this method is unable to disentangle maternal and paternal effects, which may differ in magnitude and direction. Here, we introduce an extension to the original IMPISH routine which takes advantage of all available nuclear families to impute parent-specific missing genotypes and obtain asymptotically unbiased estimates of genetic effects on offspring phenotypes. We apply this this method to data from related individuals in the UK Biobank, showing concordance with previous estimates of maternal genetic effects on offspring birthweight. We also conduct the first GWAS jointly estimating offspring-, maternal-, and paternal-specific genetic effects on body-mass index.

3.
J Dev Orig Health Dis ; : 1-6, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33272351

RESUMO

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.

4.
PLoS Genet ; 16(10): e1009154, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33104719

RESUMO

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 individual loci. In this manuscript, we illustrate how parental genetic effects on offspring phenotypes, including late onset conditions, can be estimated at individual 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 (IMputing Parental genotypes In Siblings and Half 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.

5.
Eur J Hum Genet ; 2020 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-33011735

RESUMO

Hypothesis-free Mendelian randomization studies provide a way to assess the causal relevance of a trait across the human phenome but can be limited by statistical power, sample overlap or complicated by horizontal pleiotropy. The recently described latent causal variable (LCV) approach provides an alternative method for causal inference which might be useful in hypothesis-free experiments across human phenome. We developed an automated pipeline for phenome-wide tests using the LCV approach including steps to estimate partial genetic causality, filter to a meaningful set of estimates, apply correction for multiple testing and then present the findings in a graphical summary termed causal architecture plot. We apply this pipeline to body mass index (BMI) and lipid traits as exemplars of traits where there is strong prior expectation for causal effects, and to dental caries and periodontitis as exemplars of traits where there is a need for causal inference. The results for lipids and BMI suggest that these traits are best viewed as contributing factors on a multitude of traits and conditions, thus providing additional evidence that supports viewing these traits as targets for interventions to improve health. On the other hand, caries and periodontitis are best viewed as a downstream consequence of other traits and diseases rather than a cause of ill health. The automated pipeline is implemented in the Complex-Traits Genetics Virtual Lab ( https://vl.genoma.io ) and results are available in https://view.genoma.io . We propose causal architecture plots based on phenome-wide partial genetic causality estimates as a new way visualizing the overall causal map of the human phenome.

6.
Nat Hum Behav ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989287

RESUMO

Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10-8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.

7.
Int J Cancer ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32976626

RESUMO

Alcohol consumption is correlated positively with risk for breast cancer in observational studies, but observational studies are subject to reverse causation and confounding. The association with epithelial ovarian cancer (EOC) is unclear. We performed both observational Cox regression and two-sample Mendelian randomization (MR) analyses using data from various European cohort studies (observational) and publicly available cancer consortia (MR). These estimates were compared to World Cancer Research Fund (WCRF) findings. In our observational analyses, the multivariable-adjusted hazard ratios (HR) for a one standard drink/day increase was 1.06 (95% confidence interval [CI]; 1.04, 1.08) for breast cancer and 1.00 (0.92, 1.08) for EOC, both of which were consistent with previous WCRF findings. MR ORs per genetically predicted one standard drink/day increase estimated via 34 SNPs using MR-PRESSO were 1.00 (0.93, 1.08) for breast cancer and 0.95 (0.85, 1.06) for EOC. Stratification by EOC subtype or estrogen receptor status in breast cancers made no meaningful difference to the results. For breast cancer, the CIs for the genetically derived estimates include the point-estimate from observational studies so are not inconsistent with a small increase in risk. Our data provide additional evidence that alcohol intake is unlikely to have anything other than a very small effect on risk of EOC.

8.
medRxiv ; 2020 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-32743605

RESUMO

BACKGROUND: 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. METHODS: This preregistered, cross-sectional study used a crowdsourced questionnaire in 23 languages to assess symptoms in individuals 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. RESULTS: 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 no significant 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. CONCLUSIONS: 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 (10

9.
Chem Senses ; 45(7): 609-622, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-32564071

RESUMO

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.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/complicações , Transtornos do Olfato/etiologia , Pneumonia Viral/complicações , Distúrbios Somatossensoriais/etiologia , Distúrbios do Paladar/etiologia , Adulto , Idoso , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Olfato/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/virologia , Autorrelato , Olfato , Distúrbios Somatossensoriais/virologia , Inquéritos e Questionários , Paladar , Distúrbios do Paladar/virologia , Adulto Jovem
10.
Twin Res Hum Genet ; 23(2): 123-124, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32423525

RESUMO

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.

13.
Artigo em Inglês | MEDLINE | ID: mdl-32122917

RESUMO

Most Mendelian randomization (MR) studies published in the literature to date have involved analyses of unrelated, putatively independent sets of individuals. However, estimates obtained from these sorts of studies are subject to a range of biases including dynastic effects, assortative mating, residual population stratification, and horizontal pleiotropy. The inclusion of related individuals in MR studies can help control for and, in some cases, estimate the effect of these biases on causal parameters. In this review, we discuss these biases, how they can affect MR studies, and describe three sorts of family-based study designs that can be used to control for them. We conclude that including family information from related individuals is not only possible given the world's existing twin, birth, and large-scale population-based cohorts, but likely to reap rich rewards in understanding the etiology of complex traits and diseases in the near future.

14.
Neuroimage ; 212: 116691, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32126298

RESUMO

It is well established that higher cognitive ability is associated with larger brain size. However, individual variation in intelligence exists despite brain size and recent studies have shown that a simple unifactorial view of the neurobiology underpinning cognitive ability is probably unrealistic. Educational attainment (EA) is often used as a proxy for cognitive ability since it is easily measured, resulting in large sample sizes and, consequently, sufficient statistical power to detect small associations. This study investigates the association between three global (total surface area (TSA), intra-cranial volume (ICV) and average cortical thickness) and 34 regional cortical measures with educational attainment using a polygenic scoring (PGS) approach. Analyses were conducted on two independent target samples of young twin adults with neuroimaging data, from Australia (N â€‹= â€‹1097) and the USA (N â€‹= â€‹723), and found that higher EA-PGS were significantly associated with larger global brain size measures, ICV and TSA (R2 â€‹= â€‹0.006 and 0.016 respectively, p â€‹< â€‹0.001) but not average thickness. At the regional level, we identified seven cortical regions-in the frontal and temporal lobes-that showed variation in surface area and average cortical thickness over-and-above the global effect. These regions have been robustly implicated in language, memory, visual recognition and cognitive processing. Additionally, we demonstrate that these identified brain regions partly mediate the association between EA-PGS and cognitive test performance. Altogether, these findings advance our understanding of the neurobiology that underpins educational attainment and cognitive ability, providing focus points for future research.

15.
Nutrients ; 11(10)2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31554217

RESUMO

Individuals 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 sample 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.


Assuntos
Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Comportamento Alimentar/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Olfato/efeitos dos fármacos , Paladar/efeitos dos fármacos , Humanos
16.
Int J Epidemiol ; 48(5): 1457-1467, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31335958

RESUMO

BACKGROUND: 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. METHODS: We used a novel two-sample 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 individuals; sample 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 individuals; sample 2) that enabled partitioning of the genetic associations into maternal- (intrauterine) and fetal-specific effects. RESULTS: 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)]. CONCLUSIONS: 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-sample MR in assessing the causal effect of maternal environmental exposures on offspring outcomes.


Assuntos
Peso ao Nascer , Lipídeos/sangue , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Bases de Dados Factuais , Grupo com Ancestrais do Continente Europeu , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Análise da Randomização Mendeliana , Polimorfismo de Nucleotídeo Único , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , Fatores de Risco , Triglicerídeos/sangue
17.
Am J Clin Nutr ; 109(6): 1724-1737, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31005972

RESUMO

BACKGROUND: Individual differences in human perception of sweetness are partly due to genetics; however, which genes are associated with the perception and the consumption of sweet substances remains unclear. OBJECTIVE: The aim of this study was to verify previous reported associations within genes involved in the peripheral receptor systems (i.e., TAS1R2, TAS1R3, and GNAT3) and reveal novel loci. METHODS: We performed genome-wide association scans (GWASs) of the perceived intensity of 2 sugars (glucose and fructose) and 2 high-potency sweeteners (neohesperidin dihydrochalcone and aspartame) in an Australian adolescent twin sample (n = 1757), and the perceived intensity and sweetness and the liking of sucrose in a US adult twin sample (n = 686). We further performed GWASs of the intake of total sugars (i.e., total grams of all dietary mono- and disaccharides per day) and sweets (i.e., handfuls of candies per day) in the UK Biobank sample (n = ≤174,424 white-British individuals). All participants from the 3 independent samples were of European ancestry. RESULTS: We found a strong association between the intake of total sugars and the single nucleotide polymorphism rs11642841 within the FTO gene on chromosome 16 (P = 3.8 × 10-8) and many suggestive associations (P < 1.0 × 10-5) for each of the sweet perception and intake phenotypes. We showed genetic evidence for the involvement of the brain in both sweet taste perception and sugar intake. There was limited support for the associations with TAS1R2, TAS1R3, and GNAT3 in all 3 European samples. CONCLUSIONS: Our findings indicate that genes additional to those involved in the peripheral receptor system are also associated with the sweet taste perception and intake of sweet-tasting foods. The functional potency of the genetic variants within TAS1R2, TAS1R3, and GNAT3 may be different between ethnic groups and this warrants further investigations.


Assuntos
Estudo de Associação Genômica Ampla , Glucose/metabolismo , Sacarose/metabolismo , Edulcorantes/metabolismo , Percepção Gustatória , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Criança , Feminino , Preferências Alimentares , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores Acoplados a Proteínas-G/genética , Paladar , Adulto Jovem
18.
Int J Epidemiol ; 48(3): 861-875, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30815700

RESUMO

BACKGROUND: 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 hampered by the paucity of epidemiological cohorts with large numbers of genotyped mother-offspring pairs. METHODS: 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 individual-level and summary-results data, even when the extent of sample overlap is unknown. RESULTS: We describe how the estimates obtained from our method can subsequently be used in large-scale two-sample 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 examples related to offspring birthweight and cardiometabolic disease, although the general principles we espouse are relevant for many other offspring phenotypes. CONCLUSIONS: 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-sample Mendelian randomization studies of maternal exposures and offspring outcomes.


Assuntos
Peso ao Nascer/genética , Diabetes Mellitus Tipo 2/genética , Exposição Ambiental/estatística & dados numéricos , Exposição Materna/estatística & dados numéricos , Feminino , Humanos , Análise da Randomização Mendeliana , Gravidez
19.
Behav Brain Res ; 363: 103-108, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-30703394

RESUMO

Functional neuroimaging studies have identified brain regions associated with human taste perception, but only a few have investigated the associations with brain structure. Here, in this exploratory study, we examined the association between the volumes of 82 regions of interest (ROI) and the perceived intensities of sweet (a weighted mean rating of glucose, fructose, aspartame, neohesperidin dihydrochalcone) and bitter (propylthiouracil, quinine, caffeine) substances in a large Australian healthy cohort from the Queensland Twin IMaging (QTIM, n = 559) study and the perceived intensity of quinine in a large U.S. healthy cohort from the Human Connectome Project (HCP, n = 1101). In QTIM, the volumes of 3 cortical (right cuneus gyrus, left transverse temporal gyrus, right inferior temporal gyrus) and one subcortical structure (both left and right caudate) were associated with more than one taste stimulus (P < 0.05) and tended to be associated with both sweet and bitter tastes in the same direction, suggesting these ROIs were more broadly tuned for taste sensation. A further 11 ROIs were associated with a specific taste (sweetness: 4; propylthiouracil: 3; caffeine: 2; quinine: 2). In HCP, volumes of 5 ROIs were associated with quinine bitterness. The quinine-left entorhinal cortex association was found in both QTIM (r = -0.12, P = 3.7 × 10-3) and HCP (r = -0.06, P = 2.0 × 10-2). This study provides the first evidence that, even in healthy people, variation in brain structure is associated with taste intensity ratings, and provides new insights into the brain gustatory circuit.


Assuntos
Encéfalo/patologia , Percepção Gustatória/fisiologia , Paladar/fisiologia , Adulto , Austrália , Agentes Aversivos/metabolismo , Cafeína , Conectoma , Feminino , Humanos , Masculino , Propiltiouracila , Quinina , Sacarose , Edulcorantes/metabolismo
20.
Sci Rep ; 8(1): 16414, 2018 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-30442986

RESUMO

Consumption of coffee, tea and alcohol might be shaped by individual 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 (>4 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.


Assuntos
Consumo de Bebidas Alcoólicas , Café , Análise da Randomização Mendeliana , Percepção Gustatória , Paladar , Chá , Estudos de Associação Genética , Variação Genética , Humanos , Percepção Gustatória/genética , Reino Unido
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