A Common Genetic Influence on Human Intensity Ratings of Sugars and High-Potency Sweeteners

The perception of sweetness varies among individuals but the sources of this variation are not fully understood. Here, in a sample of 1,901 adolescent and young adults (53.8% female; 243 MZ and 452 DZ twin pairs, 511 unpaired individuals; 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: h2 = 0.31, fructose: h2 = 0.34) and high-potency sweeteners (NHDC: h2 = 0.31, aspartame: h2 = 0.30); all were in the modest range. Multivariate modeling showed that a common genetic factor accounted for >75% of the genetic variance in the four sweeteners, suggesting that individual 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.

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Parental depression and offspring psychopathology: a Children of Twins study

Psychological Medicine ◽

10.1017/s0033291710002059 ◽

2010 ◽

Vol 41 (7) ◽

pp. 1385-1395 ◽

Cited By ~ 53

Author(s):

A. L. Singh ◽

B. M. D'Onofrio ◽

W. S. Slutske ◽

E. Turkheimer ◽

R. E. Emery ◽

...

Keyword(s):

Genetic Factors ◽

Parental Depression ◽

Structured Interview ◽

Disruptive Disorders ◽

Children Of Twins ◽

History Of ◽

Mz Twins ◽

History Of Depression ◽

Shared Genetic

BackgroundAssociations between parental depression and offspring affective and disruptive disorders are well documented. Few genetically informed studies have explored the processes underlying intergenerational associations.MethodA semi-structured interview assessing DSM-III-R psychiatric disorders was administered to twins (n=1296) from the Australian Twin Register (ATR), their spouses (n=1046) and offspring (n=2555). We used the Children of Twins (CoT) design to delineate the extent to which intergenerational associations were consistent with a causal influence or due to genetic confounds.ResultsIn between-family analyses, parental depression was associated significantly with offspring depression [hazard ratio (HR) 1.52, 95% confidence interval (CI) 1.20–1.93] and conduct disorder (CD; HR 2.27, CI 1.31–3.93). Survival analysis indicated that the intergenerational transmission of depression is consistent with a causal (environmental) inference, with a significant intergenerational association in offspring of discordant monozygotic (MZ) twin pairs (HR 1.39, CI 1.00–1.94). Logistic regression analysis suggested that the parental depression–offspring CD association was due to shared genetic liability in the parents and offspring. No intergenerational association was found when comparing the offspring of discordant MZ twins [odds ratio (OR) 1.41, CI 0.63–3.14], but offspring of discordant dizygotic (DZ) twins differed in their rates of CD (OR 2.53, CI 0.95–6.76). All findings remained after controlling for several measured covariates, including history of depression and CD in the twins' spouses.ConclusionsThe mechanisms underlying associations between parental depression and offspring psychopathology seem to differ depending on the outcome. The results are consistent with a causal environmental role of parental depression in offspring depression whereas common genetic factors account for the association of parental depression and offspring CD.

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A novel framework for analysis of the shared genetic background of correlated traits

10.1101/2021.12.13.472525 ◽

2021 ◽

Author(s):

Gulnara R. Svishcheva ◽

Evgeny S. Tiys ◽

Elizaveta E. Elgaeva ◽

Sofia G. Feoktistova ◽

Paul R. H. J. Timmers ◽

...

Keyword(s):

Genetic Background ◽

Genetic Variance ◽

Genetic Factors ◽

Summary Statistics ◽

Simulation Studies ◽

Correlated Traits ◽

Genetic And Phenotypic Correlations ◽

Psychiatric Conditions ◽

Variance Explained ◽

Shared Genetic

We propose a novel effective framework for analysis of the shared genetic background for a set of genetically correlated traits using SNP-level GWAS summary statistics. This framework called SHAHER is based on the construction of a linear combination of traits by maximizing the proportion of its genetic variance explained by the shared genetic factors. SHAHER requires only full GWAS summary statistics and matrices of genetic and phenotypic correlations between traits as inputs. Our framework allows both shared and unshared genetic factors to be to effectively analyzed. We tested our framework using simulation studies, compared it with previous developments, and assessed its performance using three real datasets: anthropometric traits, psychiatric conditions and lipid concentrations. SHAHER is versatile and applicable to summary statistics from GWASs with arbitrary sample sizes and sample overlaps, allows incorporation of different GWAS models (Cox, linear and logistic) and is computationally fast.

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Genomic and phenomic insights from an atlas of genetic effects on DNA methylation

10.1101/2020.09.01.20180406 ◽

2020 ◽

Author(s):

Josine L Min ◽

Gibran Hemani ◽

Eilis Hannon ◽

Koen F Dekkers ◽

Juan Castillo-Fernandez ◽

...

Keyword(s):

Dna Methylation ◽

Genetic Variants ◽

Complex Traits ◽

Genetic Architecture ◽

Genetic Variance ◽

Genetic Factors ◽

Additive Genetic Variance ◽

Genetic Influences ◽

Methylation Quantitative Trait Loci ◽

Shared Genetic

Characterizing genetic influences on DNA methylation (DNAm) provides an opportunity to understand mechanisms underpinning gene regulation and disease. Here we describe results of DNA methylation-quantitative trait loci (mQTL) analyses on 32,851 participants, identifying genetic variants associated with DNAm at 420,509 DNAm sites in blood. We present a database of >270,000 independent mQTL of which 8.5% comprise long-range (trans) associations. Identified mQTL associations explain 15-17% of the additive genetic variance of DNAm. We reveal that the genetic architecture of DNAm levels is highly polygenic and DNAm exhibits signatures of negative and positive natural selection. Using shared genetic control between distal DNAm sites we construct networks, identifying 405 discrete genomic communities enriched for genomic annotations and complex traits. Shared genetic factors are associated with both blood DNAm levels and complex diseases but in most cases these associations do not reflect causal relationships from DNAm to trait or vice versa indicating a more complex genotype-phenotype map than has previously been hypothesised.

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Incidence and familial risk of pleural mesothelioma in Sweden: a national cohort study

European Respiratory Journal ◽

10.1183/13993003.00091-2016 ◽

2016 ◽

Vol 48 (3) ◽

pp. 873-879 ◽

Cited By ~ 11

Author(s):

Jianguang Ji ◽

Jan Sundquist ◽

Kristina Sundquist

Keyword(s):

Genetic Factors ◽

Familial Risk ◽

Incidence Rates ◽

Pleural Mesothelioma ◽

Familial Clustering ◽

Swedish Cancer Registry ◽

National Cohort ◽

History Of ◽

Underlying Mechanisms ◽

Shared Genetic

Familial clustering of pleural mesothelioma was reported previously, but none of the reports quantified the familial risk of mesothelioma or the association with other cancers. The contributions of shared environmental or genetic factors to the aggregation of mesothelioma were unknown.We used a number of Swedish registers, including the Swedish Multigeneration Register and the Swedish Cancer Register, to examine the familial risk of mesothelioma in offspring. Standardised incidence ratios (SIRs) were used to calculate the risk. Age standardised incidence rates of mesothelioma were calculated from the Swedish Cancer Registry.The incidence of mesothelioma reached its peak rate in 2000 and decreased thereafter. Risk of mesothelioma was significantly increased when parents or siblings were diagnosed with mesothelioma, with SIRs of 3.88 (95% CI 1.01–10.04) and 12.37 (95% CI 5.89–22.84), respectively. Mesothelioma was associated with kidney (SIR 2.13, 95% CI 1.16–3.59) and bladder cancers (SIR 2.09, 95% CI 1.32–3.14) in siblings. No association was found between spouses.Family history of mesothelioma, including both parental and sibling history, is an important risk factor for mesothelioma. Shared genetic factors may contribute to the observed familial clustering of mesothelioma, but the contribution of shared environmental factors could not be neglected. The association with kidney and bladder cancers calls for further study to explore the underlying mechanisms.

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Genetic and environmental architecture of conscientiousness in adolescence

Scientific Reports ◽

10.1038/s41598-021-82781-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yusuke Takahashi ◽

Anqing Zheng ◽

Shinji Yamagata ◽

Juko Ando

Keyword(s):

Individual Differences ◽

Effortful Control ◽

Genetic Variance ◽

Genetic Factors ◽

Common Factor ◽

Genetic Correlations ◽

Self Control ◽

Genetic Analyses ◽

Environmental Correlations ◽

Per Se

AbstractUsing a genetically informative design (about 2000 twin pairs), we investigated the phenotypic and genetic and environmental architecture of a broad construct of conscientiousness (including conscientiousness per se, effortful control, self-control, and grit). These four different measures were substantially correlated; the coefficients ranged from 0.74 (0.72–0.76) to 0.79 (0.76–0.80). Univariate genetic analyses revealed that individual differences in conscientiousness measures were moderately attributable to additive genetic factors, to an extent ranging from 62 (58–65) to 64% (61–67%); we obtained no evidence that shared environmental influences were observed. Multivariate genetic analyses showed that for the four measures used to assess conscientiousness, genetic correlations were stronger than the corresponding non-shared environmental correlations, and that a latent common factor accounted for over 84% of the genetic variance. Our findings suggest that individual differences in the four measures of conscientiousness are not distinguishable at both the phenotypic and behavioural genetic levels, and that the overlap was substantially attributable to genetic factors.

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Cocaine use, abuse and dependence in a population-based sample of female twins

The British Journal of Psychiatry ◽

10.1192/bjp.173.4.345 ◽

1998 ◽

Vol 173 (4) ◽

pp. 345-350 ◽

Cited By ~ 113

Author(s):

Kenneth S. Kendler ◽

Carol A. Prescott

Keyword(s):

Cocaine Abuse ◽

Genetic Factors ◽

Model Fitting ◽

Population Based ◽

Cocaine Use ◽

Past Half Century ◽

History Of ◽

Population Based Registry ◽

Twin Resemblance

BackgroundAlthough cocaine use in women has increased substantially over the past half-century, we understand little about the aetiology in women of cocaine use and abuse, and know almost nothing about the role of genetic factors.MethodWe obtained by telephone interview a history of lifetime cocaine use, abuse and dependence from 1934 individual twins from female–female pairs ascertained through a population-based registry, including both members of 485 monozygotic (MZ) and 335 dizygotic (DZ) pairs.ResultsThe prevalence of lifetime cocaine use, abuse and dependence were 14.0%, 3.3% and 2.3%. Probandwise concordance rates, in MZ and DZ twins, respectively, were: cocaine use 54% and 42%; cocaine abuse 47% and 8% and cocaine dependence 35% and 0%. In MZ and DZ twins, odds ratios were: cocaine use 14.2 and 6.7 and cocaine abuse 40.8 and 2.7. Biometrical model-fitting suggested that twin resemblance for liability to cocaine use was due to both genetic and familial–environmental factors while twin resemblance for cocaine abuse and symptoms of dependence was due solely to genetic factors. Estimated heritabilities were: cocaine use 0.39, cocaine abuse 0.79 and symptoms of dependence 0.65.ConclusionsThe vulnerability to cocaine use and particularly cocaine abuse and dependence in women is substantially influenced by genetic factors.

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Luther's Word on Man's Will: A Case Study in Comparative Intellectual History

Religious Studies ◽

10.1017/s0034412500016607 ◽

1984 ◽

Vol 20 (4) ◽

pp. 657-667

Author(s):

Mark Migotti

Keyword(s):

Intellectual History ◽

Martin Luther ◽

Historical Analysis ◽

History Of Thought ◽

Thematic Unity ◽

History Of ◽

Way Of Thinking ◽

Single Set

It is commonplace to observe that the history of thought reveals certain recurring patterns whose mode of expression changes according to context. It is equally apparent that to chart the salient characteristics of an influential way of thinking – to give concrete, clearly defined shape to the usually tangled fundamental impulses informing a cast of mind – is a complex, difficult task which calls for attention from (at least) the historian, the psychologist, the philosopher and, in the case of religious figures and movements, the theologian alike. With regard to the manner of thinking embodied in the theological doctrines of Martin Luther such a task is fraught with more than the usual number of pitfalls. In the first place, following recent Luther scholarship, we must be wary of assuming that the great Reformer held fast to a single set of theological opinions throughout his long career. We shall not, therefore, attempt to reach conclusions applicable to Luther's thought as a whole, but rather shall focus exclusively on a number of key early expositions of the Theologia Crucis. Here, between about 1514 and 1520, we find, according to our argument, enough thematic unity to warrant the search for underlying principles. A second, less easily disposed of difficulty is the lack of a working consensus as to how and with what aims in mind one should even begin an historical analysis of Luther's texts. For example, to the believer who regards Luther's basic tenets as in a straightforward sense divinely inspired, the attempt to extract from his writings the ingredients of a certain thoroughly human way of thinking will seem doomed to inadequacy from the start. Likewise, for different reasons, many of today's.

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Identification of Potential Pleiotropic Genes for Immune and Skeletal Diseases Using Multivariate MetaCCA Analysis

Current Genomics ◽

10.2174/1389202923666211223115214 ◽

2021 ◽

Vol 23 ◽

Author(s):

Pei He ◽

Rong- Rong Cao ◽

Fei- Yan Deng ◽

Shu- Feng Lei

Keyword(s):

Association Study ◽

Canonical Correlation ◽

Genetic Factors ◽

Genome Wide Association Study ◽

Summary Statistics ◽

Immune Disease ◽

Histocompatibility Complex ◽

Genome Wide ◽

Genetic Mechanisms ◽

Shared Genetic

Background: Immune and skeletal systems physiologically and pathologically interact with each other. The immune and skeletal diseases may share potential pleiotropic genetics factors, but the shared specific genes are largely unknown Objective: This study aimed to investigate the overlapping genetic factors between multiple diseases (including rheumatoid arthritis (RA), psoriasis, osteoporosis, osteoarthritis, sarcopenia and fracture) Methods: The canonical correlation analysis (metaCCA) approach was used to identify the shared genes for six diseases by integrating genome-wide association study (GWAS)-derived summary statistics. Versatile Gene-based Association Study (VEGAS2) method was further applied to refine and validate the putative pleiotropic genes identified by metaCCA. Results: About 157 (p<8.19E-6), 319 (p<3.90E-6) and 77 (p<9.72E-6) potential pleiotropic genes were identified shared by two immune disease, four skeletal diseases, and all of the six diseases, respectively. The top three significant putative pleiotropic genes shared by both immune and skeletal diseases, including HLA-B, TSBP1 and TSBP1-AS1 (p<E-300) were located in the major histocompatibility complex (MHC) region. Nineteen of 77 putative pleiotropic genes identified by metaCCA analysis were associated with at least one disease in the VEGAS2 analysis. Specifically, majority (18) of these 19 putative validated pleiotropic genes were associated with RA. Conclusion: The metaCCA method identified some pleiotropic genes shared by the immune and skeletal diseases. These findings help to improve our understanding of the shared genetic mechanisms and signaling pathways underlying immune and skeletal diseases.

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Familial Aggregation of Psoriasis and Co-Aggregation of Autoimmune Diseases in Affected Families

Journal of Clinical Medicine ◽

10.3390/jcm8010115 ◽

2019 ◽

Vol 8 (1) ◽

pp. 115 ◽

Cited By ~ 5

Author(s):

Yu-Huei Huang ◽

Chang-Fu Kuo ◽

Lu-Hsiang Huang ◽

Mei-Yun Hsieh

Keyword(s):

Autoimmune Diseases ◽

Genetic Factors ◽

Familial Aggregation ◽

Population Based ◽

Study Cohort ◽

Genetic Contribution ◽

Degree Relative ◽

Nationwide Study ◽

Relative Risks ◽

History Of

Psoriasis is considered to result from the interaction of genetic factors and environmental exposure. The evidence for familial aggregation in psoriasis has been reported but population-based studies related to the magnitude of genetic contribution to psoriasis are rare. This study aimed to evaluate the relative risks of psoriasis in individuals with affected relatives and to calculate the proportion of genetic, shared, and non-shared environmental factors contributing to psoriasis. The study cohort included 69,828 patients diagnosed with psoriasis enrolled in National health Insurance in 2010. The adjusted relative risks (RR) for individuals with an affected first-degree relative and affected second-degree relative were 5.50 (95% CI (Confidence Interval), 5.19–5.82) and 2.54 (95% CI, 2.08–3.12) respectively. For those who have affected first-degree relatives, their RR was 1.45 (95% CI, 1.17–1.79) for Sjogren’s syndrome and 1.94 (95% CI, 1.15–3.27) for systemic sclerosis. This nationwide study ascertains that family history of psoriasis is a risk factor for psoriasis. Individuals with relatives affected by psoriasis have higher risks of developing some autoimmune diseases.

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Genetic and environmental influences on psychological distress in the population: General Health Questionnaire analyses in UK twins

Psychological Medicine ◽

10.1017/s0033291703007451 ◽

2003 ◽

Vol 33 (5) ◽

pp. 793-801 ◽

Cited By ~ 45

Author(s):

F. V. RIJSDIJK ◽

H. SNIEDER ◽

J. ORMEL ◽

P. SHAM ◽

D. P. GOLDBERG ◽

...

Keyword(s):

Genetic Control ◽

General Health ◽

Genetic Factors ◽

General Health Questionnaire ◽

Model Fitting ◽

Regression Method ◽

Health Questionnaire ◽

Twin Data ◽

Score Distribution ◽

Shared Genetic

Background. The General Health Questionnaire (GHQ) is the most popular screening instrument for detecting psychiatric disorders in community samples. Using longitudinal data of a large sample of UK twin pairs, we explored (i) heritabilities of the four scales and the total score; (ii) the genetic stability over time; and (iii) the existence of differential heritable influences at the high (ill) and low (healthy) tail of the distribution.Method. At baseline we assessed the GHQ in 627 MZ and 1323 DZ female pairs and at a second occasion (3·5 years later) for a small subsample (90 MZ and 270 DZ pairs). Liability threshold models and raw ordinal maximum likelihood were used to estimate twin correlations and to fit longitudinal genetic models. We estimated extreme group heritabilities of the GHQ distribution by using a model-fitting implementation of the DeFries–Fulker regression method for selected twin data.Results. Heritabilities for Somatic Symptoms, Anxiety, Social Dysfunction, Depression and total score were 0·37, 0·40, 0·20, 0·42 and 0·44, respectively. The contribution of shared genetic factors to the correlations between time points is substantial for the total score (73%). Group heritabilities of 0·48 and 0·43 were estimated for the top and bottom 10% of the total GHQ score distribution, respectively.Conclusion. The overall heritability of the GHQ as a measure of psychosocial distress was substantial (44%), with all scales having significant additive genetic influences that persisted across time periods. Extreme group analyses suggest that the genetic control of resilience is as important as the genetic control of vulnerability.

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