Open Targets Genetics: An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci

Mountjoy, Edward; Schmidt, Ellen M.; Carmona, Miguel; Peat, Gareth; Miranda, Alfredo; Fumis, Luca; Hayhurst, James; Buniello, Annalisa; Schwartzentruber, Jeremy; Karim, Mohd Anisul; Wright, Deil S.; Hercules, Andrew; Papa, Eliseo; Fauman, Eric B.; Barrett, Jeffrey C.; Todd, John; Ochoa, David; Dunham, Ian; Ghoussaini, Maya

doi:10.1101/2020.09.16.299271

Cited by 25 publications

(36 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the GWAS of SA within psychiatric diagnosis, this index SNP had a slightly smaller effect size on SA (index SNP = rs62474683, OR for A allele = 1.04 [1.01-1.07], P=0.007), but no SNPs reached genome-wide significance in this analysis. Examining the intergenic locus on chromosome 7 in published GWAS results using Open Targets Genetics web portal 59 (https://genetics.opentargets.org), showed smaller and non-significant effects on all psychiatric disorders tested (Figure 1b). However, the index SNP from our SA GWAS has been implicated at genome-wide significance in lifetime smoking index 57 (which accounts for duration and amount of smoking), and propensity towards risk-taking behavior 56 , although with smaller effect sizes than on SA (Figure 1b, Table S4-5).…”

Section: Resultsmentioning

confidence: 99%

Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

Mullins¹,

Kang²,

Campos³

et al. 2020

Preprint

View full text Add to dashboard Cite

Suicide is a leading cause of death worldwide and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both are known to have a substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium and conditioned the results on psychiatric disorders using GWAS summary statistics, to investigate their shared and divergent genetic architectures. Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated after conditioning and has previously been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, lower socioeconomic status, pain, lower educational attainment, reproductive traits, risk-taking, sleep disturbances, and poorer overall general health. After conditioning, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest the existence of a shared genetic etiology between SA and known risk factors that is not mediated by psychiatric disorders.

show abstract

Section: Resultsmentioning

confidence: 99%

Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

Mullins¹,

Kang²,

Campos³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…), interaction-based datasets (e.g., Promoter Capture Hi-C), genomic distance, and variant effect predictions (VEP) from Ensembl. A detailed description of the evidence sources and weights used is provided in the OTG documentation (https://genetics-docs.opentargets.org/our-approach/data-pipeline) 23,59 .…”

Section: Methodsmentioning

confidence: 99%

Mapping the human genetic architecture of COVID-19 by worldwide meta-analysis

Ganna

2021

Preprint

View full text Add to dashboard Cite

The genetic makeup of an individual contributes to susceptibility and response to viral infection. While environmental, clinical and social factors play a role in exposure to SARS-CoV-2 and COVID-19 disease severity, host genetics may also be important. Identifying host-specific genetic factors indicate biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-COV-2 infection and COVID-19 severity. We describe the results of three genome-wide association meta-analyses comprising 49,562 COVID-19 patients from 46 studies across 19 countries worldwide. We reported 15 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases. They also represent potentially actionable mechanisms in response to infection. We further identified smoking and body mass index as causal risk factors for severe COVID-19. The identification of novel host genetic factors associated with COVID-19, with unprecedented speed, was enabled by prioritization of shared resources and analytical frameworks. This working model of international collaboration a blue-print for future genetic discoveries in the event of pandemics or for any complex human disease.

show abstract

Section: A C C E L E R a T E D A R T I C L E P R E V I E Wmentioning

confidence: 99%

Mapping the human genetic architecture of COVID-19

Initiative

2021

Nature

Self Cite

748

643

View full text Add to dashboard Cite

Mapping the human genetic architecture of COVID-19 COVID-19 Host Genetics InitiativeThis is a PDF file of a peer-reviewed paper that has been accepted for publication. Although unedited, the content has been subjected to preliminary formatting. Nature is providing this early version of the typeset paper as a service to our authors and readers. The text and figures will undergo copyediting and a proof review before the paper is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers apply.

show abstract

Open Targets Genetics: An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci

Cited by 25 publications

References 55 publications

Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

Dissecting the shared genetic architecture of suicide attempt, psychiatric disorders and known risk factors

Mapping the human genetic architecture of COVID-19 by worldwide meta-analysis

Mapping the human genetic architecture of COVID-19

Contact Info

Product

Resources

About