scholarly journals Consortium genome-wide meta-analysis for childhood dental caries traits

2017 ◽  
Author(s):  
Simon Haworth ◽  
Dmitry Shungin ◽  
Justin T van der Tas ◽  
Strahinja Vucic ◽  
Carolina Medina Gomez ◽  
...  
Keyword(s):  
Dental Caries ◽  
Genetic Variants ◽  
Primary Teeth ◽  
Meta Analysis ◽  
Genetic Effects ◽  
Permanent Dentition ◽  
Permanent Teeth ◽  
Common Disease ◽  
Genome Wide ◽  
Common Genetic Variants

AbstractPrior studies suggest dental caries traits in children and adolescents are partially heritable, but there has been no large-scale consortium genome-wide association study (GWAS) to date. We therefore performed GWAS for caries in participants aged 2.5-18.0 years from 9 contributing centers. Phenotype definitions were created for the presence or absence of treated or untreated caries, stratified by primary and permanent dentition. All studies tested for association between caries and genotype dosage (imputed to Haplotype Reference Consortium or 1000 Genomes phase 1 version 3 panels) accounting for population stratification. Fixed–effects meta-analysis was performed weighted by inverse standard error. Analysis included up to 19,003 individuals (7,530 affected) for primary teeth and 13,353 individuals (5,875 affected) for permanent teeth. Evidence for association with caries status was observed at rs1594318-C for primary teeth (intronic within ALLC, Odds Ratio (OR) 0.85, Effect Allele Frequency (EAF) 0.60, p 4.13e-8) and rs7738851-A (intronic within NEDD9, OR 1.28, EAF 0.85, p 1.63e-8) for permanent teeth. Consortium-wide estimated heritability of caries was low (h2 of 1% [95% CI: 0%:7%] and 6% [95% CI 0%:13%] for primary and permanent dentitions, respectively) compared to corresponding within-study estimates (h2 of 28%, [95% CI: 9%:48%] and 17% [95% CI:2%:31%]) or previously published estimates. This study was designed to identify common genetic variants with modest effects which are consistent across different populations. We found few single variants associated with caries status under these assumptions. Phenotypic heterogeneity between cohorts and limited statistical power will have contributed; these findings could also reflect complexity not captured by our study design, such as genetic effects which are conditional on environmental exposure.Author summaryDental caries (tooth decay) is a common disease in children. Previous studies suggest genetic factors alter caries risk, but to date there is a gap of knowledge in identifying which specific genetic variants are responsible. We undertook analysis in a consortium including around 19,000 children and investigated whether any of 8 million common genetic variants were associated with risk of caries in primary (milk) or permanent teeth. If identified, these variants are used as ‘tags’ to highlight genes which may be involved in a disease. We identified variants in two loci associated with caries status; in the primary (rs1594318) and permanent dentition (rs7738851). The former is intronic in ALLC, a gene with poorly understood function. The latter is an intronic variant within NEDD9, a gene which has several known functions including a role in development of craniofacial structures. To gain a more comprehensive understanding of genetic effects which influence caries larger studies and a better understanding of environmental modifiers or interactions with genetic effects are required.

scholarly journals Dental caries in primary and permanent teeth in children’s worldwide, 1995 to 2019: a systematic review and meta-analysis

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Mohsen Kazeminia ◽  
Alireza Abdi ◽  
Shamarina Shohaimi ◽  
Rostam Jalali ◽  
Aliakbar Vaisi-Raygani ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dental Caries ◽  
Sample Size ◽  
Primary Teeth ◽  
Meta Analysis ◽  
Permanent Teeth ◽  
Significant Difference ◽  
The World ◽  
Review Study ◽  
Meta Regression Analysis

Abstract Background Early childhood caries (ECC) is a type of dental caries in the teeth of infants and children that is represented as one of the most prevalent dental problems in this period. Various studies have reported different types of prevalence of dental caries in primary and permanent teeth in children worldwide. However, there has been no comprehensive study to summarize the results of these studies in general, so this study aimed to determine the prevalence of dental caries in primary and permanent teeth in children in different continents of the world during a systematic review and meta-analysis. Methods In this review study, articles were extracted by searching in the national and international databases of SID, MagIran, IranMedex, IranDoc, Cochrane, Embase, ScienceDirect, Scopus, PubMed, and Web of Science (ISI) between 1995 and December 2019. Random effects model was used for analysis and heterogeneity of studies was evaluated by using the I2 index. Data were analyzed by using the Comprehensive Meta-Analysis (Version 2) software. Findings In this study, a total of 164 articles (81 articles on the prevalence of dental caries in primary teeth and 83 articles on the prevalence of dental caries in permanent teeth) were entered the meta-analysis. The prevalence of dental caries in primary teeth in children in the world with a sample size of 80,405 was 46.2% (95% CI: 41.6–50.8%), and the prevalence of dental caries in permanent teeth in children in the world with a sample size of 1,454,871 was 53.8% (95% CI: 50–57.5%). Regarding the heterogeneity on the basis of meta-regression analysis, there was a significant difference in the prevalence of dental caries in primary and permanent teeth in children in different continents of the world. With increasing the sample size and the year of study, dental caries in primary teeth increased and in permanent teeth decreased. Conclusion The results of this study showed that the prevalence of primary and permanent dental caries in children in the world was found to be high. Therefore, appropriate strategies should be implemented to improve the aforementioned situation and to troubleshoot and monitor at all levels by providing feedback to hospitals.

scholarly journals Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake

2013 ◽  
Vol 97 (6) ◽  
pp. 1395-1402 ◽  
Author(s):  
Toshiko Tanaka ◽  
Julius S Ngwa ◽  
Frank JA van Rooij ◽  
M Carola Zillikens ◽  
Mary K Wojczynski ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Observational Studies ◽  
Meta Analysis ◽  
Macronutrient Intake ◽  
Genome Wide ◽  
Common Genetic Variants

scholarly journals Meta-GWAS Accuracy and Power (MetaGAP) calculator shows that hiding heritability is partially due to imperfect genetic correlations across studies

2016 ◽  
Author(s):  
Ronald de Vlaming ◽  
Aysu Okbay ◽  
Cornelius A. Rietveld ◽  
Magnus Johannesson ◽  
Patrik K.E. Magnusson ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Fixed Effects ◽  
Statistical Power ◽  
Large Scale ◽  
Predictive Accuracy ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Genetic Effects ◽  
Missing Heritability ◽  
Genome Wide

AbstractLarge-scale genome-wide association results are typically obtained from a fixed-effects meta-analysis of GWAS summary statistics from multiple studies spanning different regions and/or time periods. This approach averages the estimated effects of genetic variants across studies. In case genetic effects are heterogeneous across studies, the statistical power of a GWAS and the predictive accuracy of polygenic scores are attenuated, contributing to the so-called ‘missing heritability’. Here, we describe the online Meta-GWAS Accuracy and Power calculator (MetaGAP; available at www.devlaming.eu) which quantifies this attenuation based on a novel multi-study framework. By means of simulation studies, we show that under a wide range of genetic architectures, the statistical power and predictive accuracy provided by this calculator are accurate. We compare the predictions from MetaGAP with actual results obtained in the GWAS literature. Specifically, we use genomic-relatedness-matrix restricted maximum likelihood (GREML) to estimate the SNP heritability and cross-study genetic correlation of height, BMI, years of education, and self-rated health in three large samples. These estimates are used as input parameters for the MetaGAP calculator. Results from the calculator suggest that cross-study heterogeneity has led to attenuation of statistical power and predictive accuracy in recent large-scale GWAS efforts on these traits (e.g., for years of education, we estimate a relative loss of 51–62% in the number of genome-wide significant loci and a relative loss in polygenic score R2 of 36–38%). Hence, cross-study heterogeneity contributes to the missing heritability.Author SummaryLarge-scale genome-wide association studies are uncovering the genetic architecture of traits which are affected by many genetic variants. Such studies typically meta-analyze association results from multiple studies spanning different regions and/or time periods. GWAS results do not yet capture a large share of the total proportion of trait variation attributable to genetic variation. The origins of this so-called ‘missing heritability’ have been strongly debated. One factor exacerbating the missing heritability is heterogeneity in the effects of genetic variants across studies. Its influence on statistical power to detect associated genetic variants and the accuracy of polygenic predictions is poorly understood. In the current study, we derive the precise effects of heterogeneity in genetic effects across studies on both the statistical power to detect associated genetic variants as well as the accuracy of polygenic predictions. We provide an online calculator, available at www.devlaming.eu, which accounts for these effects. By means of this calculator, we show that imperfect genetic correlations between studies substantially decrease statistical power and predictive accuracy and, thereby, contribute to the missing heritability. The MetaGAP calculator helps researchers to gauge how sensitive their results will be to heterogeneity in genetic effects across studies. If strong heterogeneity is expected, random-instead of fixed-effects meta-analysis methods should be used.

scholarly journals Radiogenomics Consortium Genome-Wide Association Study Meta-Analysis of Late Toxicity After Prostate Cancer Radiotherapy

2019 ◽  
Vol 112 (2) ◽  
pp. 179-190 ◽  
Author(s):  
Sarah L Kerns ◽  
Laura Fachal ◽  
Leila Dorling ◽  
Gillian C Barnett ◽  
Andrea Baran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Genetic Variants ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Urinary Frequency ◽  
Risk Models ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
Urinary Stream

Abstract Background A total of 10%–20% of patients develop long-term toxicity following radiotherapy for prostate cancer. Identification of common genetic variants associated with susceptibility to radiotoxicity might improve risk prediction and inform functional mechanistic studies. Methods We conducted an individual patient data meta-analysis of six genome-wide association studies (n = 3871) in men of European ancestry who underwent radiotherapy for prostate cancer. Radiotoxicities (increased urinary frequency, decreased urinary stream, hematuria, rectal bleeding) were graded prospectively. We used grouped relative risk models to test associations with approximately 6 million genotyped or imputed variants (time to first grade 2 or higher toxicity event). Variants with two-sided Pmeta less than 5 × 10−8 were considered statistically significant. Bayesian false discovery probability provided an additional measure of confidence. Statistically significant variants were evaluated in three Japanese cohorts (n = 962). All statistical tests were two-sided. Results Meta-analysis of the European ancestry cohorts identified three genomic signals: single nucleotide polymorphism rs17055178 with rectal bleeding (Pmeta = 6.2 × 10−10), rs10969913 with decreased urinary stream (Pmeta = 2.9 × 10−10), and rs11122573 with hematuria (Pmeta = 1.8 × 10−8). Fine-scale mapping of these three regions was used to identify another independent signal (rs147121532) associated with hematuria (Pconditional = 4.7 × 10−6). Credible causal variants at these four signals lie in gene-regulatory regions, some modulating expression of nearby genes. Previously identified variants showed consistent associations (rs17599026 with increased urinary frequency, rs7720298 with decreased urinary stream, rs1801516 with overall toxicity) in new cohorts. rs10969913 and rs17599026 had similar effects in the photon-treated Japanese cohorts. Conclusions This study increases the understanding of the architecture of common genetic variants affecting radiotoxicity, points to novel radio-pathogenic mechanisms, and develops risk models for testing in clinical studies. Further multinational radiogenomics studies in larger cohorts are worthwhile.

scholarly journals Genome-wide association meta-analysis of childhood and adolescent internalising symptoms

2020 ◽  
Author(s):  
Eshim S Jami ◽  
Anke R Hammerschlag ◽  
Hill F Ip ◽  
Andrea G Allegrini ◽  
Beben Benyamin ◽  
...  
Keyword(s):  
Confidence Intervals ◽  
Meta Analysis ◽  
Genetic Correlations ◽  
Genetic Effects ◽  
Childhood Aggression ◽  
Genome Wide Association ◽  
Childhood And Adolescence ◽  
Obsessive Compulsive ◽  
Compulsive Disorder ◽  
Genome Wide

Internalising symptoms in childhood and adolescence are as heritable as adult depression and anxiety, yet little is known of their molecular basis. This genome-wide association meta-analysis of internalising symptoms included repeated observations from 64,641 individuals, aged between 3 and 18. The N-weighted meta-analysis of overall internalising symptoms (INToverall) detected no genome-wide significant hits and showed low SNP heritability (1.66%, 95% confidence intervals 0.84-2.48%, Neffective=132,260). Stratified analyses showed rater-based heterogeneity in genetic effects, with self-reported internalising symptoms showing the highest heritability (5.63%, 95% confidence intervals 3.08-8.18%). Additive genetic effects on internalising symptoms appeared stable over age, with overlapping estimates of SNP heritability from early-childhood to adolescence. Gene-based analyses showed significant associations with three genes: WNT3 (p=1.13×10-06), CCL26 (p=1.88×10-06), and CENPO (p=2.54×10-06). Of these, WNT3 was previously associated with neuroticism, with which INToverall also shared a strong genetic correlation (rg=0.76). Genetic correlations were also observed with adult anxiety, depression, and the wellbeing spectrum (|rg|> 0.70), as well as with insomnia, loneliness, attention-deficit hyperactivity disorder, autism, and childhood aggression (range |rg|=0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Overall, childhood and adolescent internalising symptoms share substantial genetic vulnerabilities with adult internalising disorders and other childhood psychiatric traits, which could explain both the persistence of internalising symptoms over time, and the high comorbidity amongst childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.

scholarly journals Genome-wide association study identifies 48 common genetic variants associated with handedness

2019 ◽  
Author(s):  
Gabriel Cuellar Partida ◽  
Joyce Y Tung ◽  
Nicholas Eriksson ◽  
Eva Albrecht ◽  
Fazil Aliev ◽  
...  
Keyword(s):  
Association Study ◽  
Genetic Variants ◽  
Complex Traits ◽  
Genome Wide Association Study ◽  
Genetic Correlations ◽  
Genome Wide Association ◽  
Left Handedness ◽  
Left Handed ◽  
Genome Wide ◽  
Common Genetic Variants

AbstractHandedness, a consistent asymmetry in skill or use of the hands, has been studied extensively 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 32 studies from the International Handedness Consortium, we conducted the world’s largest genome-wide association study of handedness (1,534,836 right-handed, 194,198 (11.0%) left-handed and 37,637 (2.1%) ambidextrous individuals). We found 41 genetic loci associated with left-handedness and seven associated with ambidexterity at genome-wide levels of significance (P < 5×10−8). Tissue enrichment analysis implicated the central nervous system and brain tissues including the hippocampus and cerebrum in the etiology of left-handedness. Pathways including regulation of microtubules, neurogenesis, axonogenesis and hippocampus morphology were also highlighted. We found suggestive positive genetic correlations between being left-handed and some neuropsychiatric traits including schizophrenia and bipolar disorder. SNP heritability analyses indicated that additive genetic effects of genotyped variants explained 5.9% (95% CI = 5.8% – 6.0%) of the underlying liability of being left-handed, while the narrow sense heritability was estimated at 12% (95% CI = 7.2% – 17.7%). Further, we show that genetic correlation between left-handedness and ambidexterity is low (rg = 0.26; 95% CI = 0.08 – 0.43) implying that these traits are largely influenced by different genetic mechanisms. In conclusion, our findings suggest that handedness, like many other complex traits is highly polygenic, and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders that has been observed in multiple observational studies.

scholarly journals Maternal and fetal genetic contribution to gestational weight gain

2017 ◽  
Author(s):  
Nicole M Warrington ◽  
Rebecca Richmond ◽  
Bjarke Fenstra ◽  
Ronny Myhre ◽  
Romy Gaillard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Weight Gain ◽  
Gestational Weight Gain ◽  
Genetic Variants ◽  
Genetic Contribution ◽  
Gestational Weight ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
Maternal Bmi

AbstractBackgroundClinical recommendations to limit gestational weight gain (GWG) imply high GWG is causally related to adverse outcomes in mother or offspring, but GWG is the sum of several inter-related complex phenotypes (maternal fat deposition and vascular expansion, placenta, amniotic fluid and fetal growth). Understanding the genetic contribution to GWG could help clarify the potential effect of its different components on maternal and offspring health. Here we explore the genetic contribution to total, early and late GWG.Participants and MethodsA genome-wide association study was used to identify maternal and fetal variants contributing to GWG in up to 10,543 mothers and up to 16,317 offspring of European origin, with replication in 10,660 mothers and 7,561 offspring. Additional analyses determined the proportion of variability in GWG from maternal and fetal common genetic variants and the overlap of established genome-wide significant variants for phenotypes relevant to GWG (e.g. maternal BMI and glucose, birthweight).ResultsWe found that approximately 20% of the variability in GWG was tagged by common maternal genetic variants, and that the fetal genome made a surprisingly minor contribution to explaining variation in GWG. We were unable to identify any genetic variants that reached genome-wide levels of significance (P<5×10−8) and replicated. Some established maternal variants associated with increased BMI, fasting glucose and type 2 diabetes were associated with lower early, and higher later GWG. Maternal variants related to higher systolic blood pressure were related to lower late GWG. Established maternal and fetal birthweight variants were largely unrelated to GWG.ConclusionWe found a modest contribution of maternal common variants to GWG and some overlap of maternal BMI, glucose and type 2 diabetes variants with GWG. These findings suggest that associations between GWG and later offspring/maternal outcomes may be due to the relationship of maternal BMI and diabetes with GWG.

scholarly journals Association of genetic variants in enamel-formation genes with dental caries: A meta- and gene-cluster analysis

2020 ◽  
Author(s):  
Xueyan Li ◽  
DI LIU ◽  
Sun Yang ◽  
Jingyun Yang ◽  
Youcheng Yu
Keyword(s):  
Cluster Analysis ◽  
Dental Caries ◽  
Gene Cluster ◽  
Genetic Variants ◽  
Literature Search ◽  
Genetic Variant ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Systematic Literature Search ◽  
Enamel Formation

Previous studies have reported the association between multiple genetic variants in enamel formation-related genes and the risk of dental caries with inconsistent results. We performed a systematic literature search of the PubMed, Cochrane Library, HuGE and Google Scholar databases for studies published before March 21, 2020 and conducted meta-, gene-based and gene-cluster analysis on the association between genetic variants in enamel- formation-related genes and the risk of dental caries. Our systematic literature search identified 21 relevant publications including a total of 24 studies for analysis. The genetic variant rs17878486 in AMELX was significantly associated with dental caries risk (OR=1.40, 95% CI: 1.02-1.93, P=0.037). We found no significant association between the risk of dental caries with rs12640848 in ENAM (OR=1.15, 95% CI: 0.88-1.52, P=0.310), rs1784418 in MMP20 (OR=1.07, 95% CI: 0.76-1.49, P=0.702) and rs3796704 in ENAM (OR=1.06, 95% CI: 0.96-1.17, P=0.228). Gene-based analysis indicated that multiple genetic variants in AMELX showed joint association with the risk of dental caries (6 variants; P<10-5), so did genetic variants in MMP13 (3 variants; P=0.004), MMP2 (3 variants; P<10-5), MMP20 (2 variants; P<10-5) and MMP3 (2 variants; P<10-5). The gene-cluster analysis indicated a significant association between the genetic variants in this enamel-formation gene cluster and the risk of dental caries (P<10-5). The present meta-analysis revealed that genetic variant rs17878486 in AMELX were associated with dental caries, and multiple genetic variants in enamel-formation-related genes jointly contribute to the risk of dental caries, supporting the role of genetic variants in the enamel-formation genes in the etiology of dental caries.

Statistical Genetics

2018 ◽  
pp. 57-69 ◽  
Author(s):  
Till F. M. Andlauer ◽  
Bertram Müller-Myhsok ◽  
Stephan Ripke
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Meta Analysis ◽  
Power Calculation ◽  
Genome Wide Association Studies ◽  
Psychiatric Genetics ◽  
Factors Influencing ◽  
Genome Wide ◽  
Basic Concepts ◽  
Study Designs

Over more than the last decade, hypothesis-free genome-wide association studies (GWAS) have been widely used to detect genetic factors influencing phenotypes of interest. The basic principle of GWAS has been unchanged since the beginning: a series of univariate tests is conducted on all genetic variants available across the genome. We present study designs and commonly used methods for genome-wide studies, with a focus on the analysis of common variants. The basic concepts required for an application of GWAS in psychiatric genetics are introduced, from power calculation to meta-analysis. This chapter will help the reader in gaining the knowledge required for participation in and realization of GWAS of both qualitative and quantitative traits.

Sign in / Sign up

Export Citation Format

Share Document