scholarly journals Non-Syndromic Cleft Lip with or without Cleft Palate: Genome-Wide Association Study in Europeans Identifies a Suggestive Risk Locus at 16p12.1 and Supports SH3PXD2A as a Clefting Susceptibility Gene

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 1023 ◽  
Author(s):  
Iris ALM van Rooij ◽  
Kerstin U Ludwig ◽  
Julia Welzenbach ◽  
Nina Ishorst ◽  
Michelle Thonissen ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Susceptibility Gene ◽  
Small Sample ◽  
Genome Wide Association ◽  
P Value ◽  
Genome Wide ◽  
A Genome

Non-syndromic cleft lip with or without cleft palate (nsCL/P) ranks among the most common human congenital malformations, and has a multifactorial background in which both exogenous and genetic risk factors act in concert. The present report describes a genome-wide association study (GWAS) involving a total of 285 nsCL/P patients and 1212 controls from the Netherlands and Belgium. Twenty of the 40 previously reported nsC/LP susceptibility loci were replicated, which underlined the validity of this sample. SNV-based analysis of the data identified an as yet unreported suggestive locus at chromosome 16p12.1 (p-value of the lead SNV: 4.17 × 10−7). This association was replicated in two of three patient/control replication series (Central European and Yemeni). Gene analysis of the GWAS data prioritized SH3PXD2A at chromosome 10q24.33 as a candidate gene for nsCL/P. To date, support for this gene as a cleft gene has been restricted to data from zebrafish and a knockout mouse model. The present GWAS was the first to implicate SH3PXD2A in non-syndromic cleft formation in humans. In summary, although performed in a relatively small sample, the present GWAS generated novel insights into nsCL/P etiology.

scholarly journals Erratum: A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

2010 ◽  
Vol 42 (8) ◽  
pp. 727-727 ◽  
Author(s):  
Terri H Beaty ◽  
Jeffrey C Murray ◽  
Mary L Marazita ◽  
Ronald G Munger ◽  
Ingo Ruczinski Jacqueline B Hetmanski ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Risk Variants ◽  
Genome Wide ◽  
A Genome

A Genome-Wide Association Study Identifies a Locus for Nonsyndromic Cleft Lip with or without Cleft Palate on 8q24

2009 ◽  
Vol 155 (6) ◽  
pp. 909-913 ◽  
Author(s):  
Struan F.A. Grant ◽  
Kai Wang ◽  
Haitao Zhang ◽  
Wendy Glaberson ◽  
Kiran Annaiah ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

scholarly journals A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

2010 ◽  
Vol 42 (6) ◽  
pp. 525-529 ◽  
Author(s):  
Terri H Beaty ◽  
Jeffrey C Murray ◽  
Mary L Marazita ◽  
Ronald G Munger ◽  
Ingo Ruczinski ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Risk Variants ◽  
Genome Wide ◽  
A Genome

scholarly journals Genome-wide association study of antipsychotic-induced sinus bradycardia in Chinese schizophrenia patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249997
Author(s):  
Saizheng Weng ◽  
Bo Wang ◽  
Mo Li ◽  
Shan Chao ◽  
Ruiqian Lin ◽  
...  
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Sinus Bradycardia ◽  
Susceptibility Gene ◽  
Han Chinese ◽  
Genome Wide Association ◽  
Genome Wide ◽  
A Genome

Second-generation antipsychotics (SGAs) play a critical role in current treatment of schizophrenia (SCZ). It has been observed that sinus bradycardia, rare but in certain situations life threatening adverse drug reaction, can be induced by SGAs across different schizophrenia populations. However, the roles of genetic factors in this phenomenon have not been studied yet. In the present study, a genome-wide association study of single nucleotide polymorphisms (SNPs) was performed on Chinese Han SCZ patients to identify susceptibility loci that were associated with sinus bradycardia induced by SGAs. This study applied microarray to obtain genotype profiles of 88 Han Chinese SCZ patients. Our results found that there were no SNPs had genome-wide significant association with sinus bradycardia induced by SGAs. The top GWAS hit located in gene KIAA0247, which mainly regulated by the tumor suppressor P53 and thus plays a role in carcinogenesis based on resent research and it should not be a susceptibility locus to sinus bradycardia induced by SGAs. Using gene-set functional analysis, we tested that if top 500 SNPs mapped genes were relevant to sinus bradycardia. The result of gene prioritization analysis showed CTNNA3 was strongly correlated with sinus bradycardia, hinting it was a susceptibility gene of this ADR. Our study provides a preliminary study of genetic variants associated with sinus bradycardia induced by SGAs in Han Chinese SCZ patients. The discovery of a possible susceptibility gene shed light on further study of this adverse drug reaction in Han Chinese SCZ patients.

scholarly journals Genome-wide association study identifies two susceptibility loci for nonsyndromic cleft lip with or without cleft palate

2009 ◽  
Vol 42 (1) ◽  
pp. 24-26 ◽  
Author(s):  
Elisabeth Mangold ◽  
Kerstin U Ludwig ◽  
Stefanie Birnbaum ◽  
Carlotta Baluardo ◽  
Melissa Ferrian ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Association Study ◽  
Cleft Lip ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Susceptibility Loci ◽  
Genome Wide

scholarly journals Genome-wide association study of alcohol consumption and genetic overlap with other health-related traits in UK Biobank (N=112,117)

2017 ◽  
Author(s):  
Toni-Kim Clarke ◽  
Mark J. Adams ◽  
Gail Davies ◽  
David M. Howard ◽  
Lynsey S. Hall ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Hdl Cholesterol ◽  
Genome Wide Association ◽  
P Value ◽  
Uk Biobank ◽  
Genome Wide ◽  
A Genome ◽  
Genetic Overlap

AbstractAlcohol consumption has been linked to over 200 diseases and is responsible for over 5% of the global disease burden. Well known genetic variants in alcohol metabolizing genes, e.g. ALDH2, ADH1B, are strongly associated with alcohol consumption but have limited impact in European populations where they are found at low frequency. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 112,117 individuals in the UK Biobank (UKB) sample of white British individuals. We report significant genome-wide associations at 8 independent loci. These include SNPs in alcohol metabolizing genes (ADH1B/ADH1C/ADH5) and 2 loci in KLB, a gene recently associated with alcohol consumption. We also identify SNPs at novel loci including GCKR, PXDN, CADM2 and TNFRSF11A. Gene-based analyses found significant associations with genes implicated in the neurobiology of substance use (CRHR1, DRD2), and genes previously associated with alcohol consumption (AUTS2). GCTA-GREML analyses found a significant SNP-based heritability of self-reported alcohol consumption of 13% (S.E.=0.01). Sex-specific analyses found largely overlapping GWAS loci and the genetic correlation between male and female alcohol consumption was 0.73 (S.E.=0.09, p-value = 1.37 x 10−16). Using LD score regression, genetic overlap was found between alcohol consumption and schizophrenia (rG=0.13, S.E=0.04), HDL cholesterol (rG=0.21, S.E=0.05), smoking (rG=0.49, S.E=0.06) and various anthropometric traits (e.g. Overweight, rG=-0.19, S.E.=0.05). This study replicates the association between alcohol consumption and alcohol metabolizing genes and KLB, and identifies 4 novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.

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