An atlas of genetic associations in UK Biobank

Canela-Xandri, Oriol; Rawlik, Konrad; Tenesa, Albert

doi:10.1038/s41588-018-0248-z

Cited by 510 publications

(399 citation statements)

References 22 publications

(21 reference statements)

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“…At the gene level, overrepresentation enrichment analysis (ORA) with WebGestalt67 on the nearest genes to all BP loci was carried out. Moreover, we tested sentinel SNPs at all published and novel (N=901) loci for association with lifestyle related data including food, water and alcohol intake, anthropomorphic traits and urinary sodium, potassium and creatinine excretion using the recently developed Stanford Global Biobank Engine and the Gene ATLAS68. Both are search engines for GWAS findings for multiple phenotypes in UK Biobank.…”

Section: Methodsmentioning

confidence: 99%

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Εvangelou¹,

Warren²,

et al. 2018

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High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic, pulse pressure) to date in over one million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also reveal shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.

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Section: Methodsmentioning

confidence: 99%

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Εvangelou¹,

Warren²,

et al. 2018

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“…GeneATLAS (https://geneatlas.roslin.ed.ac.uk/; The Roslin Institute, Edinburgh, UK) is an online searchable database of summary genetic associations based on data from the UK Biobank . GeneATLAS included data from 452,264 UK Biobank participants of white British descent.…”

Section: Methodsmentioning

confidence: 99%

“…Several groups of researchers have been granted access to the full UK Biobank database, including all traits and genotypes. Two groups, Rivas and colleagues and Tenesa and colleagues, ran GWAS across thousands of UK Biobank traits. The summary results from these analyses were made available to the scientific community through user‐friendly online browsers in mid‐2017.…”

mentioning

confidence: 99%

Identification and Replication of Six Loci Associated With Gallstone Disease

et al. 2019

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Gallstone disease is a common complex disease that confers a substantial economic burden on society. The genetic underpinnings of gallstone disease remain incompletely understood. We aimed to identify genetic associations with gallstone disease using publicly available data from the UK Biobank and two large Danish cohorts. We extracted genetic associations with gallstone disease from the Global Biobank Engine (GBE), an online browser of genome‐wide associations in UK Biobank participants (14,940 cases and 322,268 controls). Significant associations (P < 5 × 10–8) were retested in two Copenhagen cohorts (comprising 1,522 cases and 18,266 controls). In the Copenhagen cohorts, we also tested whether a genetic risk score was associated with gallstone disease and whether individual gallstone loci were associated with plasma levels of lipids, lipoproteins, and liver enzymes. We identified 19 loci to be associated with gallstone disease in the GBE. Of these, 12 were replicated in the Copenhagen cohorts, including six previously unknown loci (in hepatocyte nuclear factor 4 alpha [HNF4A], fucosyltransferase 2, serpin family A member 1 [SERPINA1], jumonji domain containing 1C, AC074212.3, and solute carrier family 10A member 2 [SLC10A2]) and six known loci (in adenosine triphosphate binding cassette subfamily G member 8 [ABCG8], sulfotransferase family 2A member 1, cytochrome P450 7A1, transmembrane 4 L six family member 4, ABCB4, and tetratricopeptide repeat domain 39B). Five of the gallstone associations are protein‐altering variants, and three (HNF4A p.Thr139Ile, SERPINA1 p.Glu366Lys, and SLC10A2 p.Pro290Ser) conferred per‐allele odds ratios for gallstone disease of 1.30‐1.36. Individuals with a genetic risk score >2.5 (prevalence 1%) had a 5‐fold increased risk of gallstones compared to those with a score <1.0 (11%). Of the 19 lithogenic loci, 11 and ten exhibited distinct patterns of association with plasma levels of lipids and liver enzymes, respectively. Conclusion: We identified six susceptibility loci for gallstone disease.

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“…COGA participants were recruited from extended families, most of which were ascertained for alcohol dependence. 25 Further, any GWS associations with ANYDEP in the EA sample were tested for association with alcohol intake among 452 264 individuals from the UK Biobank 26 and cannabis use from a meta-analysis conducted on 184 765 individuals. 22, 23 We conducted ancestry-specific analyses in EAs and AAs followed by a transancestral meta-analysis (EA + AA) to identify loci associated with ANYDEP, that is, dependence on any one or a combination of alcohol, cannabis, cocaine, sedatives, stimulants and/or opioids.…”

Section: Introductionmentioning

confidence: 99%

Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans

Wetherill

Lai

Johnson

et al. 2019

Genes Brain and Behavior

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Genetic influences on alcohol and drug dependence partially overlap, however, specific loci underlying this overlap remain unclear. We conducted a genome‐wide association study (GWAS) of a phenotype representing alcohol or illicit drug dependence (ANYDEP) among 7291 European‐Americans (EA; 2927 cases) and 3132 African‐Americans (AA: 1315 cases) participating in the family‐based Collaborative Study on the Genetics of Alcoholism. ANYDEP was heritable (h 2 in EA = 0.60, AA = 0.37). The AA GWAS identified three regions with genome‐wide significant (GWS; P < 5E‐08) single nucleotide polymorphisms (SNPs) on chromosomes 3 (rs34066662, rs58801820) and 13 (rs75168521, rs78886294), and an insertion‐deletion on chromosome 5 (chr5:141988181). No polymorphisms reached GWS in the EA. One GWS region (chromosome 1: rs1890881) emerged from a trans‐ancestral meta‐analysis (EA + AA) of ANYDEP, and was attributable to alcohol dependence in both samples. Four genes (AA: CRKL, DZIP3, SBK3; EA: P2RX6) and four sets of genes were significantly enriched within biological pathways for hemostasis and signal transduction. GWS signals did not replicate in two independent samples but there was weak evidence for association between rs1890881 and alcohol intake in the UK Biobank. Among 118 AA and 481 EA individuals from the Duke Neurogenetics Study, rs75168521 and rs1890881 genotypes were associated with variability in reward‐related ventral striatum activation. This study identified novel loci for substance dependence and provides preliminary evidence that these variants are also associated with individual differences in neural reward reactivity. Gene discovery efforts in non‐European samples with distinct patterns of substance use may lead to the identification of novel ancestry‐specific genetic markers of risk.

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An atlas of genetic associations in UK Biobank

Cited by 510 publications

References 22 publications

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits

Identification and Replication of Six Loci Associated With Gallstone Disease

Genome‐wide association study identifies loci associated with liability to alcohol and drug dependence that is associated with variability in reward‐related ventral striatum activity in African‐ and European‐Americans

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