scholarly journals 1163 Genome-wide Association Study Reveals 55 Loci Associated with Gallstone Disease

2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
C Fairfield ◽  
A Spiliopoulou ◽  
S Wigmore ◽  
E Harrison
Keyword(s):  
Association Study ◽  
Functional Annotation ◽  
Genome Wide Association Study ◽  
Gallstone Formation ◽  
Serum Biomarkers ◽  
Genome Wide Association ◽  
Gallbladder Motility ◽  
European Ancestry ◽  
Genome Wide ◽  
A Genome

Abstract Aim Gallstones have a prevalence of 20-40% in European populations and cause significant morbidity. Gallstones form from cholesterol and calcium bilirubinate and knowledge of genetic determinants remains incomplete. A genome-wide association study (GWAS) was performed to identify determinants of gallstones. Method A GWAS of 16,356,211 single nucleotide polymorphisms (SNPs) for 28,627 cases and 348,373 controls of European ancestry in the UK Biobank was undertaken. A logistic regression with additive allelic dosage was performed (significance: P < 5*10-8). Functional annotation and linkage disequilibrium clumping were performed to reveal distinct loci. Lead SNPs were investigated by linear regression for association with plasma lipids, liver enzymes and blood count markers. Results 55 lithogenic loci were identified of which 27 are novel. Functional annotation revealed genes involved in metabolism of cholesterol, glucose, bile acids and bilirubin with corresponding changes in serum biomarkers caused by those lithogenic alleles. Several novel variants did not alter cholesterol or other biomarkers. Lithogenic variants within genes controlling intra- and paracellular transport may govern biliary composition (PCDHB4, NUP153, CLDN7) and promote lithogenic bile. Variants within genes which may influence gallbladder motility (ANO1, TMEM147) and cholangiocyte ciliogenesis (TBC1D32, ADAMTS20, DYNC2LI1, HNF1B) may promote gallstone formation through reduced biliary flow. Conclusions We identified 27 novel associations with gallstones. Impact of lithogenic alleles on serum biomarkers was highly variable demonstrating that gallstone formation is partially driven by pathways which do not influence cholesterol, glucose or bilirubin metabolism. Variants within genes that may influence biliary composition, bile flow and gallbladder motility represent new targets for research into gallstones.

scholarly journals Genome-wide association study identifies locus at chromosome 2q32.1 associated with syncope and collapse

2019 ◽  
Vol 116 (1) ◽  
pp. 138-148 ◽  
Author(s):  
Katra Hadji-Turdeghal ◽  
Laura Andreasen ◽  
Christian M Hagen ◽  
Gustav Ahlberg ◽  
Jonas Ghouse ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Psychiatric Research ◽  
Carrier Status ◽  
Genome Wide ◽  
Common Genetic Variants ◽  
A Genome ◽  
Significant Locus

Abstract Aims Syncope is a common condition associated with frequent hospitalization or visits to the emergency department. Family aggregation and twin studies have shown that syncope has a heritable component. We investigated whether common genetic variants predispose to syncope and collapse. Methods and results We used genome-wide association data on syncope on 408 961 individuals with European ancestry from the UK Biobank study. In a replication study, we used the Integrative Psychiatric Research Consortium (iPSYCH) cohort (n = 86 189), to investigate the risk of incident syncope stratified by genotype carrier status. We report on a genome-wide significant locus located on chromosome 2q32.1 [odds ratio = 1.13, 95% confidence interval (CI) 1.10–1.17, P = 5.8 × 10−15], with lead single nucleotide polymorphism rs12465214 in proximity to the gene zinc finger protein 804a (ZNF804A). This association was also shown in the iPSYCH cohort, where homozygous carriers of the C allele conferred an increased hazard ratio (1.30, 95% CI 1.15–1.46, P = 1.68 × 10−5) of incident syncope. Quantitative polymerase chain reaction analysis showed ZNF804A to be expressed most abundantly in brain tissue. Conclusion We identified a genome-wide significant locus (rs12465214) associated with syncope and collapse. The association was replicated in an independent cohort. This is the first genome-wide association study to associate a locus with syncope and collapse.

Abstract 051: Genome-wide Association Study Identifies 12 Loci for Habitual Consumption of Bitter and Sweet Beverages

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Victor W Zhong ◽  
Sandra Sanchez-Roige ◽  
Peter Kraft ◽  
Rob M Van Dam ◽  
Daniel I Chasman ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genetic Model ◽  
Taste Perception ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Multiple Snps ◽  
Genome Wide ◽  
A Genome

Introduction: Widely consumed beverages (e.g., soft drinks, coffee, tea) are critical sources of energy, added sugar and phytochemicals and are associated with obesity and chronic disease. Taste perception and preferences are highly heritable and strong determinants of food and beverage choice. We aimed to identify novel loci underlying habitual bitter and sweet beverage intake. Methods: We performed a genome-wide association study (GWAS) of self-reported bitter and sweet beverage intake in participants of European ancestry in the UK Biobank. Diet was assessed via multiple 24-h diet recalls (n=84703, subset) or questionnaire (n=335909, all). Bitter beverage intake was the sum of coffee, tea and grapefruit juice. Sweet beverage intake was the sum of artificially and sugar sweetened beverages and other fruit juice. Multivariable linear regression under an additive genetic model was applied. GW-significant (P < 5х10 -8 ) SNPs were followed-up for replication in independent studies of European ancestry. Results: Multiple SNPs spanning 11 loci were associated with bitter beverage intake (P <5х10 -8 , Table 1), and at least 5 of them reflected the caffeine content of coffee and tea. Multiple SNPs in the obesity candidate gene FTO were associated with sweet beverage intake (P <5х10 -8 ). The effect size per allele ranged from 0.02 to 0.2 cup per day. Loci in/near AHR, CYP1A2, and FTO were associated with both bitter and sweet beverage intake but in opposite directions. Replication efforts are ongoing. So far, associations at all loci, except 1q25.2 and 2q36.2, were replicated (P range: 0.04 to 1.8x10 -8 ) in independent studies (n=17322) which provided 80% power for replicating 8 of these 12 loci at P=0.05. Conclusions: Loci linked to caffeine metabolism and obesity predisposition rather than taste are major determinants of beverage intake. These and other identified loci have been linked to chronic disease and risk factors, suggesting causal or pleiotropic effects. Our findings have potential public health and methodological implications.

scholarly journals THU0464 A genome-wide association study of gout in people of european ancestry

2017 ◽  
Author(s):  
TR Merriman ◽  
M Cadzow ◽  
M Merriman ◽  
A Phipps-Green ◽  
R Topless ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide ◽  
A Genome

A genome-wide association study of depressive symptoms in women of European ancestry

2010 ◽  
Vol 51 (6) ◽  
pp. e3
Author(s):  
M.C. Cornelis ◽  
J. Agnew-Blais ◽  
P. Kraft ◽  
D. Hunter ◽  
M. Jensen ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide ◽  
A Genome

scholarly journals Multiethnic genome-wide association study of differentiated thyroid cancer in the EPITHYR consortium

2020 ◽  
Author(s):  
Therese TRUONG ◽  
Fabienne Lesueur ◽  
Pierre-emmanuel Sugier ◽  
Julie Guibon ◽  
Constance Xhaard ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Differentiated Thyroid Carcinoma ◽  
Incidence Rates ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Risk Alleles ◽  
Genome Wide ◽  
A Genome ◽  
High Incidence

Incidence of differentiated thyroid carcinoma (DTC) varies considerably between ethnic groups, with particularly high incidence rates in Pacific Islanders. Here, we conducted a genome-wide association study (GWAS) involving 1,554 cases/1,973 controls of European ancestry and 301 cases/348 controls of Oceanian ancestry from the EPITHYR consortium. Our results confirmed the association with the known DTC susceptibility loci at 2q35, 8p12, 9q22.33 and 14q13.3 in the European ancestry population and suggested two novel signals at 1p31.3 (rs334729) and 16q23.2 (rs16950982), which were associated with TSH levels in previous GWAS. We additionally replicated an association with 5p15.33 reported previously in Chinese and European populations. Except at 1p31.3, all associations were in the same direction in the population of Oceanian ancestry. The frequency of risk alleles at 2q35, 5p15.33 and 16q23.2 were significantly higher in Oceanians than in Europeans and may explain part of the highest DTC incidence observed in Oceanians.

scholarly journals Genome-wide association study of delay discounting in 23,217 adult research participants of European ancestry

2017 ◽  
Author(s):  
Sandra Sanchez-Roige ◽  
Pierre Fontanillas ◽  
Sarah L. Elson ◽  
Anita Pandit ◽  
Ellen M. Schmidt ◽  
...  
Keyword(s):  
Body Weight ◽  
Association Study ◽  
Delay Discounting ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Research Participants ◽  
Hyperactivity Disorder ◽  
Genome Wide ◽  
A Genome

ABSTRACTDelay discounting (DD), which is the tendency to discount the value of delayed versus current rewards, is elevated in a constellation of diseases and behavioral conditions. We performed a genome-wide association study of DD using 23,127 research participants of European ancestry. The most significantly associated SNP was rs6528024 (P = 2.40 × 10−8), which is located in an intron of the gene GPM6B. We also showed that 12% of the variance in DD was accounted for by genotype, and that the genetic signature of DD overlapped with attention-deficit/hyperactivity disorder, schizophrenia, major depression, smoking, personality, cognition, and body weight.

scholarly journals A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Astros Th. Skuladottir ◽  
Gyda Bjornsdottir ◽  
Muhammad Sulaman Nawaz ◽  
Hannes Petersen ◽  
Solvi Rognvaldsson ◽  
...  
Keyword(s):  
Association Study ◽  
Hearing Impairment ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Sequence Variants ◽  
Age Related ◽  
Genome Wide ◽  
A Genome

AbstractVertigo is the leading symptom of vestibular disorders and a major risk factor for falls. In a genome-wide association study of vertigo (Ncases = 48,072, Ncontrols = 894,541), we uncovered an association with six common sequence variants in individuals of European ancestry, including missense variants in ZNF91, OTOG, OTOGL, and TECTA, and a cis-eQTL for ARMC9. The association of variants in ZNF91, OTOGL, and OTOP1 was driven by an association with benign paroxysmal positional vertigo. Using previous reports of sequence variants associating with age-related hearing impairment and motion sickness, we found eight additional variants that associate with vertigo. Although disorders of the auditory and the vestibular system may co-occur, none of the six genome-wide significant vertigo variants were associated with hearing loss and only one was associated with age-related hearing impairment. Our results uncovered sequence variants associating with vertigo in a genome-wide association study and implicated genes with known roles in inner ear development, maintenance, and disease.

scholarly journals Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

2019 ◽  
Vol 7 (1) ◽  
pp. 20-34 ◽  
Author(s):  
Nick Shrine ◽  
Michael A Portelli ◽  
Catherine John ◽  
María Soler Artigas ◽  
Neil Bennett ◽  
...  
Keyword(s):  
Association Study ◽  
Severe Asthma ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide ◽  
A Genome
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