scholarly journals Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate

2017 ◽  
Vol 173 (6) ◽  
pp. 1531-1538 ◽  
Author(s):  
Elizabeth J. Leslie ◽  
Jenna C. Carlson ◽  
John R. Shaffer ◽  
Carmen J. Buxó ◽  
Eduardo E. Castilla ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Association Studies ◽  
Low Frequency ◽  
Frequency Coding ◽  
Coding Variants

scholarly journals Assessing the contribution of rare-to-common protein-coding variants to circulating metabolic biomarker levels via 412,394 UK Biobank exome sequences

2021 ◽  
Author(s):  
Abhishek Nag ◽  
Lawrence Middleton ◽  
Ryan S Dhindsa ◽  
Dimitrios Vitsios ◽  
Eleanor M Wigmore ◽  
...  
Keyword(s):  
Gene Networks ◽  
Rare Variants ◽  
Association Studies ◽  
Low Frequency ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Protein Coding ◽  
The Uk ◽  
Metabolic Biomarkers ◽  
Coding Variants

Genome-wide association studies have established the contribution of common and low frequency variants to metabolic biomarkers in the UK Biobank (UKB); however, the role of rare variants remains to be assessed systematically. We evaluated rare coding variants for 198 metabolic biomarkers, including metabolites assayed by Nightingale Health, using exome sequencing in participants from four genetically diverse ancestries in the UKB (N=412,394). Gene-level collapsing analysis, that evaluated a range of genetic architectures, identified a total of 1,303 significant relationships between genes and metabolic biomarkers (p<1x10-8), encompassing 207 distinct genes. These include associations between rare non-synonymous variants in GIGYF1 and glucose and lipid biomarkers, SYT7 and creatinine, and others, which may provide insights into novel disease biology. Comparing to a previous microarray-based genotyping study in the same cohort, we observed that 40% of gene-biomarker relationships identified in the collapsing analysis were novel. Finally, we applied Gene-SCOUT, a novel tool that utilises the gene-biomarker association statistics from the collapsing analysis to identify genes having similar biomarker fingerprints and thus expand our understanding of gene networks.

Low-frequency coding variants associated with body-mass-index impact the success of bariatric surgery

2021 ◽  
Author(s):  
Darlène Antoine ◽  
Rosa-Maria Guéant-Rodriguez ◽  
Jean-Claude Chèvre ◽  
Sébastien Hergalant ◽  
Tanmay Sharma ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Body Mass Index ◽  
Morbid Obesity ◽  
General Population ◽  
Body Mass ◽  
Intervention Program ◽  
Low Frequency ◽  
European Ancestry ◽  
Frequency Coding ◽  
Coding Variants

Abstract Context A recent study identified 14 low-frequency coding variants associated with body-mass-index (BMI) in 718,734 individuals predominantly of European ancestry. Objective and design The 14 low-frequency coding variants were genotyped or sequenced in 342 French adults with severe/morbid obesity and 574 French adult controls from the general population. We built risk and protective genetic scores (GS) based on 6 BMI-increasing and 5 BMI-decreasing low-frequency coding variants that were polymorphic in our study. We investigated the association of the two GS with i) the risk of severe/morbid obesity, ii) BMI variation before weight-loss intervention, iii) BMI change in response to an 18-month lifestyle/behavioral intervention program, and iv) BMI change up to 24 months after bariatric surgery. Results While the risk GS was not associated with severe/morbid obesity status, BMI-decreasing low-frequency coding variants were significantly less frequent in patients with severe/morbid obesity than in French adults from the general population. Neither the risk nor the protective GS was associated with BMI before intervention in patients with severe/morbid obesity, nor did they impact BMI change in response to a lifestyle/behavioral modification program. The protective GS was associated with a greater BMI decrease following bariatric surgery. The risk and protective GS were associated with a higher and lower risk of BMI regain after bariatric surgery. Conclusion Our data indicate that in populations of European descent, low-frequency coding variants associated with BMI in the general population also impact the outcomes of bariatric surgery in patients with severe/morbid obesity.

scholarly journals Investigation of candidate genes of non-syndromic cleft lip with or without cleft palate, using both case–control and family-based association studies

Medicine ◽  
2019 ◽  
Vol 98 (26) ◽  
pp. e16170 ◽  
Author(s):  
Xing Ge ◽  
Jia-Wei Hong ◽  
Jun-Yu Shen ◽  
Zheng Li ◽  
Rui Zhang ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Candidate Genes ◽  
Cleft Lip ◽  
Association Studies ◽  
Case Control ◽  
Family Based

Genetic contribution for non-syndromic cleft lip with or without cleft palate (NS CL/P) in different regions of Brazil and implications for association studies

2011 ◽  
Vol 155 (7) ◽  
pp. 1581-1587 ◽  
Author(s):  
Luciano A. Brito ◽  
Lucas A. Cruz ◽  
Kátia M. Rocha ◽  
Ligia K. Barbara ◽  
Camila B.F. Silva ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Association Studies ◽  
Genetic Contribution

scholarly journals Novel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate

2018 ◽  
Vol 55 (5) ◽  
pp. 736-742 ◽  
Author(s):  
Lord Jephthah Joojo Gowans ◽  
Ganiyu Oseni ◽  
Peter A. Mossey ◽  
Wasiu Lanre Adeyemo ◽  
Mekonen A. Eshete ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Soft Palate ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Sequence Data ◽  
Regulatory Elements ◽  
The Face ◽  
Sub Saharan ◽  
African Patients ◽  
Coding Variants

Objective: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. Patients and Method: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. Results: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. Conclusion: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P.

scholarly journals Multi-trait association studies discover pleiotropic loci between Alzheimer's disease and cardiometabolic traits

2020 ◽  
Author(s):  
William Paul Bone ◽  
Katherine M Siewert ◽  
Anupama Jha ◽  
Derek Klarin ◽  
Scott M Damrauer ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Association Studies ◽  
Low Frequency ◽  
Tissue Expression ◽  
Genome Wide Association Studies ◽  
Frequency Coding ◽  
Increased Risk ◽  
Hypertensive Drug ◽  
Cardiometabolic Traits

Identification of genetic risk factors that are shared between Alzheimer's disease (AD) and other traits, i.e., pleiotropy, can help improve our understanding of the etiology of AD and potentially detect new therapeutic targets. Motivated by previous epidemiological correlations observed between cardiometabolic traits and AD, we performed a set of bivariate genome-wide association studies coupled with colocalization analysis to identify loci that are shared between AD and eleven cardiometabolic traits. We identified three previously unreported pleiotropic trait associations at known AD loci as well as four novel pleiotropic loci. One associated locus was tagged by a low-frequency coding variant in the gene DOCK4 and is potentially implicated in its alternative splicing. Statistical colocalization with expression quantitative trait loci identified by the Genotype-Tissue Expression (GTEx) project identified additional candidate genes, including ACE, the target of the hypertensive drug class of ACE-inhibitors. We found that the allele associated with decreased ACE expression in brain tissue was also associated with increased risk of AD, providing human genetic evidence of a potential increase in AD risk from use of an established anti-hypertensive therapeutic. Overall, our results support a complex genetic relationship between AD and these cardiometabolic traits, and the candidate causal genes identified suggest that blood pressure and immune response play a role in the pleiotropy between these traits.

scholarly journals Exclusion of candidate genes from a role in cleft lip with or without cleft palate: linkage and association studies.

1993 ◽  
Vol 30 (9) ◽  
pp. 773-778 ◽  
Author(s):  
G M Vintiner ◽  
K K Lo ◽  
S E Holder ◽  
R M Winter ◽  
S Malcolm
Keyword(s):  
Cleft Palate ◽  
Candidate Genes ◽  
Cleft Lip ◽  
Association Studies

scholarly journals Rare and low-frequency coding variants alter human adult height

Nature ◽  
2017 ◽  
Vol 542 (7640) ◽  
pp. 186-190 ◽  
Author(s):  
Eirini Marouli ◽  
◽  
Mariaelisa Graff ◽  
Carolina Medina-Gomez ◽  
Ken Sin Lo ◽  
...  
Keyword(s):  
Adult Height ◽  
Low Frequency ◽  
Human Adult ◽  
Frequency Coding ◽  
Coding Variants
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