scholarly journals Genome-wide scanning versus candidate gene approach in the genetic architecture of common diseases.

2008 ◽  
Author(s):  
Carlos Pirola ◽  
Carlos Pirola ◽  
Silvia Sookoian
Keyword(s):  
Candidate Gene ◽  
Genetic Architecture ◽  
Candidate Gene Approach ◽  
Common Diseases ◽  
Genome Wide

scholarly journals Candidate gene scan for Single Nucleotide Polymorphisms involved in the determination of normal variability in human craniofacial morphology

2016 ◽  
Author(s):  
Mark Barash ◽  
Philipp E. Bayer ◽  
Angela van Daal
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Candidate Gene ◽  
Genetic Variants ◽  
Massively Parallel Sequencing ◽  
Craniofacial Morphology ◽  
Candidate Gene Approach ◽  
Nucleotide Polymorphisms ◽  
Genetic Associations ◽  
Single Nucleotide ◽  
Genome Wide

AbstractDespite intensive research on genetics of the craniofacial morphology using animal models and human craniofacial syndromes, the genetic variation that underpins normal human facial appearance is still largely elusive. Recent development of novel digital methods for capturing the complexity of craniofacial morphology in conjunction with high-throughput genotyping methods, show great promise for unravelling the genetic basis of such a complex trait.As a part of our efforts on detecting genomic variants affecting normal craniofacial appearance, we have implemented a candidate gene approach by selecting 1,201 single nucleotide polymorphisms (SNPs) and 4,732 tag SNPs in over 170 candidate genes and intergenic regions. We used 3-dimentional (3D) facial scans and direct cranial measurements of 587 volunteers to calculate 104 craniofacial phenotypes. Following genotyping by massively parallel sequencing, genetic associations between 2,332 genetic markers and 104 craniofacial phenotypes were tested.An application of a Bonferroni–corrected genome–wide significance threshold produced significant associations between five craniofacial traits and six SNPs. Specifically, associations of nasal width with rs8035124 (15q26.1), cephalic index with rs16830498 (2q23.3), nasal index with rs37369 (5q13.2), transverse nasal prominence angle with rs59037879 (10p11.23) and rs10512572 (17q24.3), and principal component explaining 73.3% of all the craniofacial phenotypes, with rs37369 (5p13.2) and rs390345 (14q31.3) were observed.Due to over-conservative nature of the Bonferroni correction, we also report all the associations that reached the traditional genome-wide p-value threshold (<5.00E-08) as suggestive. Based on the genome-wide threshold, 8 craniofacial phenotypes demonstrated significant associations with 34 intergenic and extragenic SNPs. The majority of associations are novel, except PAX3 and COL11A1 genes, which were previously reported to affect normal craniofacial variation.This study identified the largest number of genetic variants associated with normal variation of craniofacial morphology to date by using a candidate gene approach, including confirmation of the two previously reported genes. These results enhance our understanding of the genetics that determines normal variation in craniofacial morphology and will be of particular value in medical and forensic fields.Author SummaryThere is a remarkable variety of human facial appearances, almost exclusively the result of genetic differences, as exemplified by the striking resemblance of identical twins. However, the genes and specific genetic variants that affect the size and shape of the cranium and the soft facial tissue features are largely unknown. Numerous studies on animal models and human craniofacial disorders have identified a large number of genes, which may regulate normal craniofacial embryonic development.In this study we implemented a targeted candidate gene approach to select more than 1,200 polymorphisms in over 170 genes that are likely to be involved in craniofacial development and morphology. These markers were genotyped in 587 DNA samples using massively parallel sequencing and analysed for association with 104 traits generated from 3-dimensional facial images and direct craniofacial measurements. Genetic associations (p-values<5.00E-08) were observed between 8 craniofacial traits and 34 single nucleotide polymorphisms (SNPs), including two previously described genes and 26 novel candidate genes and intergenic regions. This comprehensive candidate gene study has uncovered the largest number of novel genetic variants affecting normal facial appearance to date. These results will appreciably extend our understanding of the normal and abnormal embryonic development and impact our ability to predict the appearance of an individual from a DNA sample in forensic criminal investigations and missing person cases.

scholarly journals The Genetics of Seborrheic Dermatitis: A Candidate Gene Approach and Pilot Genome-Wide Association Study

2018 ◽  
Vol 138 (4) ◽  
pp. 991-993 ◽  
Author(s):  
Martijn G.H. Sanders ◽  
Luba M. Pardo ◽  
André G. Uitterlinden ◽  
Adrian M. Smith ◽  
Rebecca S. Ginger ◽  
...  
Keyword(s):  
Association Study ◽  
Candidate Gene ◽  
Genome Wide Association Study ◽  
Seborrheic Dermatitis ◽  
Genome Wide Association ◽  
Candidate Gene Approach ◽  
Genome Wide

scholarly journals Association between Genetic Variants and Cisplatin-Induced Nephrotoxicity: A Genome-Wide Approach and Validation Study

2021 ◽  
Vol 11 (11) ◽  
pp. 1233
Author(s):  
Zulfan Zazuli ◽  
Corine de de Jong ◽  
Wei Xu ◽  
Susanne J. H. Vijverberg ◽  
Rosalinde Masereeuw ◽  
...  
Keyword(s):  
Candidate Gene ◽  
Genetic Risk ◽  
Validation Cohort ◽  
Genotype Imputation ◽  
Candidate Gene Approach ◽  
Genetic Associations ◽  
Discovery Cohort ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Significance

This study aims to evaluate genetic risk factors for cisplatin-induced nephrotoxicity by investigating not previously studied genetic risk variants and further examining previously reported genetic associations. A genome-wide study (GWAS) was conducted in genetically estimated Europeans in a discovery cohort of cisplatin-treated adults from Toronto, Canada, followed by a candidate gene approach in a validation cohort from the Netherlands. In addition, previously reported genetic associations were further examined in both the discovery and validation cohorts. The outcome, nephrotoxicity, was assessed in two ways: (i) decreased estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI) and (ii) increased serum creatinine according to the Common Terminology Criteria for Adverse Events v4.03 for acute kidney injury (AKI-CTCAE). Four different Illumina arrays were used for genotyping. Standard quality control was applied for pre- and post-genotype imputation data. In the discovery cohort (n = 608), five single-nucleotide polymorphisms (SNPs) reached genome-wide significance. The A allele in rs4388268 (minor allele frequency = 0.23), an intronic variant of the BACH2 gene, was consistently associated with increased risk of cisplatin-induced nephrotoxicity in both definitions, meeting genome-wide significance (β = −8.4, 95% CI −11.4–−5.4, p = 3.9 × 10−8) for decreased eGFR and reaching suggestive association (OR = 3.9, 95% CI 2.3–6.7, p = 7.4 × 10−7) by AKI-CTCAE. In the validation cohort of 149 patients, this variant was identified with the same direction of effect (eGFR: β = −1.5, 95% CI −5.3–2.4, AKI-CTCAE: OR = 1.7, 95% CI 0.8–3.5). Findings of our previously published candidate gene study could not be confirmed after correction for multiple testing. Genetic predisposition of BACH2 (rs4388268) might be important in the development of cisplatin-induced nephrotoxicity, indicating opportunities for mechanistic understanding, tailored therapy and preventive strategies.

scholarly journals Genetic variants related to physical activity or sedentary behaviour: a systematic review

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Lene Aasdahl ◽  
Tom Ivar Lund Nilsen ◽  
Ingebrigt Meisingset ◽  
Anne Lovise Nordstoga ◽  
Kari Anne I. Evensen ◽  
...  
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Candidate Gene ◽  
Sedentary Behaviour ◽  
Genetic Variants ◽  
Candidate Gene Approach ◽  
Genome Wide Association Studies ◽  
High Quality ◽  
Genome Wide ◽  
Candidate Gene Studies

Abstract Background Research shows that part of the variation in physical activity and sedentary behaviour may be explained by genetic factors. Identifying genetic variants associated with physical activity and sedentary behaviour can improve causal inference in physical activity research. The aim of this systematic review was to provide an updated overview of the evidence of genetic variants associated with physical activity or sedentary behaviour. Methods We performed systematic literature searches in PubMed and Embase for studies published from 1990 to April 2020 using keywords relating to “physical activity”, “exercise”, “sedentariness” and “genetics”. Physical activity phenotypes were either based on self-report (e.g., questionnaires, diaries) or objective measures (e.g., accelerometry, pedometer). We considered original studies aiming to i) identify new genetic variants associated with physical activity or sedentary behaviour (i.e., genome wide association studies [GWAS]), or ii) assess the association between known genetic variants and physical activity or sedentary behaviour (i.e., candidate gene studies). Study selection, data extraction, and critical appraisal were carried out by independent researchers, and risk of bias and methodological quality was assessed for all included studies. Results Fifty-four out of 5420 identified records met the inclusion criteria. Six of the included studies were GWAS, whereas 48 used a candidate gene approach. Only one GWAS and three candidate gene studies were considered high-quality. The six GWAS discovered up to 10 single nucleotide polymorphisms (SNPs) associated with physical activity or sedentariness that reached genome-wide significance. In total, the candidate gene studies reported 30 different genes that were associated (p < 0.05) with physical activity or sedentary behaviour. SNPs in or close to nine candidate genes were associated with physical activity or sedentary behaviour in more than one study. Conclusion GWAS have reported up to 10 loci associated with physical activity or sedentary behaviour. Candidate gene studies have pointed to some interesting genetic variants, but few have been replicated. Our review highlights the need for high-quality GWAS in large population-based samples, and with objectively assessed phenotypes, in order to establish robust genetic instruments for physical activity and sedentary behaviour. Furthermore, consistent replications in GWAS are needed to improve credibility of genetic variants. Trial registration Prospero CRD42019119456.

scholarly journals Genome-Wide Association Studies Identify 15 Genetic Markers Associated with Marmite Taste Preference

2017 ◽  
Author(s):  
Thomas R. Roos ◽  
Nikolay A. Kulemin ◽  
Ildus I. Ahmetov ◽  
Avi Lasarow ◽  
Keith Grimaldi
Keyword(s):  
Candidate Gene ◽  
Genetic Markers ◽  
Bitter Taste ◽  
Taste Preference ◽  
Genome Wide Association ◽  
Candidate Gene Approach ◽  
Genome Wide ◽  
Human Trait ◽  
Genome Wide Significance ◽  
Complex Human Trait

AbstractMarmite is a popular food eaten around the world, to which individuals have commonly considered themselves either “lovers” or “haters”. We aimed to determine whether this food preference has a genetic basis.Weperformed a genome-wide association study (GWAS) for Marmite taste preference using genotype and questionnaire data froma cohort of 261 healthy adults. We found 1 single nucleotide polymorphism (SNP) associated with Marmite taste preferencethat reached genome-wide significance (p<5x10-8) in our GWAS analyses. We found another 4 SNPsassociated with Marmite taste preference that reached genome-wide significance (p<5x10-8) in at leastoneGWAS and/or for at least one phenotype analysed. Moreover, we identified 10 additional SNPs potentially associated with Marmite taste preference through candidate gene analysis. Our results indicate that there is a genetic basis to Marmite taste preference and we have identified 15 genetic markers for this trait. Overall, we conclude that Marmite tastepreference is a complex human trait influenced by multiple genetic markers, as well as the environment.Summary of Main ResultsMarmite taste preference is a complex human trait with many factors influencing whether an individual loves or hates Marmite.The relative contribution of genetics versus environment (ie. heritability) for Marmite taste preference is unknown.The genetic contribution to Marmite taste preference involves multiple genetic markers each contributing a small amount (ie. the trait is polygenic). There is not one single Marmite gene with a large contribution like in thecase of the TAS2R38gene and bitter taste perception.We have found a total of 15 SNPs associated with Marmite taste preference: 5 SNPs by a genetic-association screen atgenome-wide significance, and 10 SNPs by a candidate gene approach at nominal significance.We did not find an association between the TAS2R38bitter taste receptor gene and Marmite taste preference.It is important to independently replicate the findings of this study in order to validate these genetic markers and get a more accurate idea of their true effect on Marmite taste preference.

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