Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure.
Ontology highlight
ABSTRACT:
SUBMITTER: Visconti A
PROVIDER: S-EPMC5940788 | biostudies-literature | 2018 May
REPOSITORIES: biostudies-literature
Publications
Genome-wide association study in 176,678 Europeans reveals genetic loci for tanning response to sun exposure.
Visconti Alessia A Duffy David L DL Liu Fan F Zhu Gu G Wu Wenting W Chen Yan Y Hysi Pirro G PG Zeng Changqing C Sanna Marianna M Iles Mark M MM Kanetsky Peter A PA Demenais Florence F Hamer Merel A MA Uitterlinden Andre G AG Ikram M Arfan MA Nijsten Tamar T Martin Nicholas G NG Kayser Manfred M Spector Tim D TD Han Jiali J Bataille Veronique V Falchi Mario M
Nature communications 20180508 1
The skin's tendency to sunburn rather than tan is a major risk factor for skin cancer. Here we report a large genome-wide association study of ease of skin tanning in 176,678 subjects of European ancestry. We identify significant association with tanning ability at 20 loci. We confirm previously identified associations at six of these loci, and report 14 novel loci, of which ten have never been associated with pigmentation-related phenotypes. Our results also suggest that variants at the AHR/AGR ...[more]
Similar Datasets
Project description:Background: Until now, the relevance of the tanning response to sun exposure and skin diseases has incomplete and inconsistent epidemiological observations. In this case, it is valuable to find out the causality of tanning response to sun exposure and skin diseases, and take a step further toward developing effective therapies as well as prevention methods. Methods: We investigated the causal effect of tanning response to sun exposure on 10 major skin diseases that have been studied in recent large-scale genome-wide association studies (GWASs). Significant independent genetic variants from large-scale GWAS on ease of skin tanning (N = 453,065) are selected as the effective instrumental variables (IVs). For each skin disease, we extracted the summary statistics of those IVs (or their proxies) from the corresponding skin disease-GWAS as the valid IVs. Mendelian randomization (MR) was further performed to evaluate the causal association of ease of skin tanning with each of the skin diseases using different statistical methods, including inverse-variance weighted (IVW), the weighted median, and MR-Egger. Sensitivity analysis was also conducted to evaluate the effect of horizontal pleiotropy and heterogeneity. Results: We observe significant associations between six skin diseases with tanning response to sun exposure with adjusted p-value derived by IVW less than 0.05 and with nominal p value less than 0.05 at the same time derived by either MR-Egger or weighted median. The six skin diseases include actinic keratosis (IVW FDR = 1.71E-40, MR Egger p-value = 3.46E-22), seborrhoeic keratosis (IVW FDR = 2.97E-4, MR Egger p-value = 1.06E-3), blepharochalasis (IVW FDR = 1.30E-3, MR Egger p-value = 2.91E-4), seborrhoeic dermatitis (IVW FDR = 1.29E-2, MR Egger p-value = 1.23E-2), malignant melanoma of skin (IVW FDR = 2.95E-2, MR Egger p-value = 1.91E-2), and freckles (IVW FDR = 2.95E-2, weighted median p-value = 1.02E-3). Interestingly, we find increased trends of developing all of the six skin diseases with increased tanning response to sun exposure (beta values are positive using IVW, MR-egger, and weighted median methods). We also replicate the association on three skin diseases using an independent outcome GWAS cohort, including malignant melanoma of the skin (replication IVW p-value = 2.13E-39), actinic keratosis (replication IVW p-value = 4.64E-32), and seborrhoeic keratosis (replication IVW p-value = 1.79E-3). Conclusion: Our observation shows that the tanning response to sun exposure is positively correlated with the development of skin diseases in people of European descent by Mendelian randomization studies. But randomized controlled trials are still needed to add proof to our observations.
| S-EPMC9478173 | biostudies-literature
Project description:Inter-individual variation in facial shape is one of the most noticeable phenotypes in humans, and it is clearly under genetic regulation; however, almost nothing is known about the genetic basis of normal human facial morphology. We therefore conducted a genome-wide association study for facial shape phenotypes in multiple discovery and replication cohorts, considering almost ten thousand individuals of European descent from several countries. Phenotyping of facial shape features was based on landmark data obtained from three-dimensional head magnetic resonance images (MRIs) and two-dimensional portrait images. We identified five independent genetic loci associated with different facial phenotypes, suggesting the involvement of five candidate genes--PRDM16, PAX3, TP63, C5orf50, and COL17A1--in the determination of the human face. Three of them have been implicated previously in vertebrate craniofacial development and disease, and the remaining two genes potentially represent novel players in the molecular networks governing facial development. Our finding at PAX3 influencing the position of the nasion replicates a recent GWAS of facial features. In addition to the reported GWA findings, we established links between common DNA variants previously associated with NSCL/P at 2p21, 8q24, 13q31, and 17q22 and normal facial-shape variations based on a candidate gene approach. Overall our study implies that DNA variants in genes essential for craniofacial development contribute with relatively small effect size to the spectrum of normal variation in human facial morphology. This observation has important consequences for future studies aiming to identify more genes involved in the human facial morphology, as well as for potential applications of DNA prediction of facial shape such as in future forensic applications.
| S-EPMC3441666 | biostudies-literature
Project description:BackgroundThe disease caused by Riemerella anatipestifer (R. anatipestifer, RA) results in large economic losses to the global duck industry every year. Serovar-related genomic variation, such as the O-antigen and capsular polysaccharide (CPS) gene clusters, has been widely used for serotyping in many gram-negative bacteria. RA has been classified into at least 21 serovars based on slide agglutination, but the molecular basis of serotyping is unknown. In this study, we performed a pan-genome-wide association study (Pan-GWAS) to identify the genetic loci associated with RA serovars.ResultsThe results revealed a significant association between the putative CPS synthesis gene locus and the serological phenotype. Further characterization of the CPS gene clusters in 11 representative serovar strains indicated that they were highly diverse and serovar-specific. The CPS gene cluster contained the key genes wzx and wzy, which are involved in the Wzx/Wzy-dependent pathway of CPS synthesis. Similar CPS loci have been found in some other species within the family Weeksellaceae. We have also shown that deletion of the wzy gene in RA results in capsular defects and cross-agglutination.ConclusionsThis study indicates that the CPS synthesis gene cluster of R. anatipestifer is a serotype-specific genetic locus. Importantly, our finding provides a new perspective for the systematic analysis of the genetic basis of the R anatipestifer serovars and a potential target for establishing a complete molecular serotyping scheme.
| S-EPMC10787497 | biostudies-literature
Project description:BackgroundResearch suggests there may be a genetic influence on the likelihood of becoming tanning dependent (TD). The way in which mothers regulate their children's sun exposure may be affected by being TD. We investigated the associations between single nucleotide polymorphisms (SNPs) related to being TD and early sun exposure.MethodsData from the Avon Longitudinal Study of Parents and Children (ALSPAC) were used. Associations between 17 TD related SNPs in children and their mothers and 10 sun exposure variables in children (assessed via questionnaire at age 8) were analyzed in logistic and ordinal logistic regressions. Analyses were adjusted for principal components of population structure and age (at time of questionnaire response). Models with additional adjustment for maternal or offspring genotypes were also tested. Secondary analyses included adjustment for sex and skin pigmentation.ResultsAmong ALSPAC children, the rs29132 SNP in the Vesicle-associated membrane protein-associated protein A (VAPA) gene was associated with five sun exposure variables whilst the rs650662 SNP in the Opioid Receptor Mu 1 (OPRM1) gene was associated with three. The remaining SNPs did not show associations beyond what was expected by chance. After Bonferroni correction one SNP in the children was associated with an increased likelihood of using sun cream whilst in the sun at 8 years old (rs60050811 in the Spermatogenesis and Centriole Associated 1 (SPATC1) gene, OR per C allele = 1.34, 95% CI 1.11-1.62, p = .003). In the mothers, rs650662 in OPRM1 was associated with the use of a lower factor of sun cream in their children, (OR per A allele = 0.89, 95% CI 0.82-0.96, p = .002). Whilst rs2073478 in the Aldehyde Dehydrogenase 1 Family Member B1 (ALDH1B1) gene was associated with a reduced odds of their child using a sun block or cream with a 4 star rating (OR per T allele = 0.68, 95% CI 0.53-0.88, p = .003). Similar but weaker associations were observed for the main findings in the secondary analyses.ConclusionsWe found weak evidence to suggest that genes previously associated with TD are associated with sun exposure in children of European ancestry from southwest England.
| S-EPMC5898059 | biostudies-literature
Project description: Not available
| S-EPMC3190399 | biostudies-literature
Project description:Objectives: We present patterns of sunburn, sun safety behaviors and indoor tanning bed use in a nationally representative sample of schoolchildren aged 10-17. These behaviors were explored across gender, age, and social class groups. Methods: Within the Health Behaviour in School-aged Children (HBSC) Ireland study, 10,271 young people (aged 13.54 ± 1.92, percentage girls 53.3%) reported frequency of sun safety behaviors, sunburn, and frequency and circumstances of indoor tanning bed use. Results: Children frequently experienced sunburn (90% lifetime, 74% last year), and 3% reported never using any sun protection. Applying sunscreen and wearing sunglasses were the most commonly used sun safety measures; other ways of sun protection were less popular. Indoor tanning bed use was reported by around 5%, and a large proportion of users were not advised of any indoor tanning safety measures. Sun safety behaviors varied by age and gender, with some socio-economic differences in tanning bed use. An association was found between frequency of family holidays abroad and sunburn. Conclusion: Targeted interventions are needed to increase sun safety behaviors and eliminate tanning bed use among children in Ireland.
| S-EPMC8284860 | biostudies-literature
Project description:OBJECTIVE:Average daily gain (ADG) is an important target trait of pig breeding programs. We aimed to identify single nucleotide polymorphisms (SNPs) and genomic regions that are associated with ADG in the Duroc pig population. METHODS:We performed a genome-wide association study involving 390 Duroc boars and by using the PorcineSNP60K Beadchip and two linear models. RESULTS:After quality control, we detected 3,5971 SNPs, which included seven SNPs that are significantly associated with the ADG of pigs. We identified six quantitative trait loci (QTL) regions for ADG. These QTLs included four previously reported QTLs on Sus scrofa chromosome (SSC) 1, SSC5, SSC9, and SSC13, as well as two novel QTLs on SSC6 and SSC16. In addition, we selected six candidate genes (general transcription factor 3C polypeptide 5, high mobility group AT-hook 2, nicotinamide phosphoribosyltransferase, oligodendrocyte transcription factor 1, pleckstrin homology and RhoGEF domain containing G4B, and ENSSSCG00000031548) associated with ADG on the basis of their physiological roles and positional information. These candidate genes are involved in skeletal muscle cell differentiation, diet-induced obesity, and nervous system development. CONCLUSION:This study contributes to the identification of the casual mutation that underlies QTLs associated with ADG and to future pig breeding programs based on marker-assisted selection. Further studies are needed to elucidate the role of the identified candidate genes in the physiological processes involved in ADG regulation.
| S-EPMC5838319 | biostudies-literature
Project description:Climate change causes increased tree mortality leading to canopy loss and thus sun-exposed forest floors. Sun exposure creates extreme temperatures and radiation, with potentially more drastic effects on forest organisms than the current increase in mean temperature. Such conditions might potentially negatively affect the maturation of mushrooms of forest fungi. A failure of reaching maturation would mean no sexual spore release and, thus, entail a loss of genetic diversity. However, we currently have a limited understanding of the quality and quantity of mushroom-specific molecular responses caused by sun exposure. Thus, to understand the short-term responses toward enhanced sun exposure, we exposed mushrooms of the wood-inhabiting forest species Lentinula edodes, while still attached to their mycelium and substrate, to artificial solar light (ca. 30°C and 100,000 lux) for 5, 30, and 60 min. We found significant differentially expressed genes at 30 and 60 min. Eukaryotic Orthologous Groups (KOG) class enrichment pointed to defense mechanisms. The 20 most significant differentially expressed genes showed the expression of heat-shock proteins, an important family of proteins under heat stress. Although preliminary, our results suggest mushroom-specific molecular responses to tolerate enhanced sun exposure as expected under climate change. Whether mushroom-specific molecular responses are able to maintain fungal fitness under opening forest canopies remains to be tested.
| S-EPMC8328440 | biostudies-literature
Project description:BackgroundParkinson's disease (PD) and schizophrenia (SCZ) are heritable brain disorders that involve dysregulation of the dopaminergic system. Epidemiological studies have reported potential comorbidity between the disorders, and movement disturbances are common in patients with SCZ before treatment with antipsychotic drugs. Despite this, little is known about shared genetic etiology between the disorders.MethodsWe analyzed recent large genome-wide association studies on patients with SCZ (N = 77,096) and PD (N = 417,508) using a conditional/conjunctional false discovery rate (FDR) approach to evaluate overlap in common genetic variants and improve statistical power for genetic discovery. Using a variety of biological resources, we functionally characterized the identified genomic loci.ResultsWe observed genetic enrichment in PD conditional on associations with SCZ and vice versa, indicating polygenic overlap. We then leveraged this cross-trait enrichment using conditional FDR analysis and identified 9 novel PD risk loci and 1 novel SCZ locus at conditional FDR < .01. Furthermore, we identified 9 genomic loci jointly associated with PD and SCZ at conjunctional FDR < .05. There was an even distribution of antagonistic and agonistic effect directions among the shared loci, in line with the insignificant genetic correlation between the disorders. Of 67 genes mapped to the shared loci, 65 are expressed in the human brain and show cell type-specific expression profiles.ConclusionsAltogether, the study increases understanding of the genetic architectures underlying SCZ and PD, indicating that common molecular genetic mechanisms may contribute to overlapping pathophysiological and clinical features between the disorders.
| S-EPMC7416467 | biostudies-literature
Project description:Host genetics, an important contributor to the COVID-19 clinical susceptibility and severity, currently is the focus of multiple genome-wide association studies (GWAS) in populations affected by the pandemic. This is the first study from Serbia that performed a GWAS of COVID-19 outcomes to identify genetic risk markers of disease severity. A group of 128 hospitalized COVID-19 patients from the Serbian population was enrolled in the study. We conducted a GWAS comparing (1) patients with pneumonia (n = 80) against patients without pneumonia (n = 48), and (2) severe (n = 34) against mild disease (n = 48) patients, using a genotyping array followed by imputation of missing genotypes. We have detected a significant signal associated with COVID-19 related pneumonia at locus 13q21.33, with a peak residing upstream of the gene KLHL1 (p = 1.91 × 10−8). Our study also replicated a previously reported COVID-19 risk locus at 3p21.31, identifying lead variants in SACM1L and LZTFL1 genes suggestively associated with pneumonia (p = 7.54 × 10−6) and severe COVID-19 (p = 6.88 × 10−7), respectively. Suggestive association with COVID-19 pneumonia has also been observed at chromosomes 5p15.33 (IRX, NDUFS6, MRPL36, p = 2.81 × 10−6), 5q11.2 (ESM1, p = 6.59 × 10−6), and 9p23 (TYRP1, LURAP1L, p = 8.69 × 10−6). The genes located in or near the risk loci are expressed in neural or lung tissues, and have been previously associated with respiratory diseases such as asthma and COVID-19 or reported as differentially expressed in COVID-19 gene expression profiling studies. Our results revealed novel risk loci for pneumonia and severe COVID-19 disease which could contribute to a better understanding of the COVID-19 host genetics in different populations.
| S-EPMC9329799 | biostudies-literature