2021
Genome-wide functional screen of 3′UTR variants uncovers causal variants for human disease and evolution
Griesemer D, Xue JR, Reilly SK, Ulirsch JC, Kukreja K, Davis JR, Kanai M, Yang DK, Butts JC, Guney MH, Luban J, Montgomery SB, Finucane HK, Novina CD, Tewhey R, Sabeti PC. Genome-wide functional screen of 3′UTR variants uncovers causal variants for human disease and evolution. Cell 2021, 184: 5247-5260.e19. PMID: 34534445, PMCID: PMC8487971, DOI: 10.1016/j.cell.2021.08.025.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesCausal variantsEvolutionary adaptationGenome-wide functional screenDiverse molecular mechanismsHuman evolutionary adaptationBase-pair resolutionParallel reporterHuman cell linesMiRNA sitesTranscriptional changesFunctional screenAllelic replacementSimple sequenceMolecular mechanismsAssociation studiesRich elementsPair resolutionHuman diseasesPhenotype associationsHuman traitsUntranslated region variantsGenetic variantsRegulatory activityCell linesFunctional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation
Khetan S, Kales S, Kursawe R, Jillette A, Ulirsch JC, Reilly SK, Ucar D, Tewhey R, Stitzel ML. Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation. Nature Communications 2021, 12: 5242. PMID: 34475398, PMCID: PMC8413311, DOI: 10.1038/s41467-021-25514-6.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesSingle nucleotide polymorphismsTranscriptional activationEndoplasmic reticulum (ER) stress conditionsTranscriptional stress responseCis-regulatory effectsParallel reporter assaysT2D single nucleotide polymorphismsHigh linkage disequilibriumMultiple single nucleotide polymorphismsT2D genetic riskT2D-associated single nucleotide polymorphismsMIN6 β-cellsChromatin accessibilityCandidate single nucleotide polymorphismsT2D geneticsHuman genomeAssociation signalsRepetitive elementsFunctional characterizationNuclear elementsMolecular mechanismsReporter assaysStress responseAssociation studies
2020
Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features
Ray JP, de Boer CG, Fulco CP, Lareau CA, Kanai M, Ulirsch JC, Tewhey R, Ludwig LS, Reilly SK, Bergman DT, Engreitz JM, Issner R, Finucane HK, Lander ES, Regev A, Hacohen N. Prioritizing disease and trait causal variants at the TNFAIP3 locus using functional and genomic features. Nature Communications 2020, 11: 1237. PMID: 32144282, PMCID: PMC7060350, DOI: 10.1038/s41467-020-15022-4.Peer-Reviewed Original ResearchConceptsChromatin accessible regionsGenome-wide association studiesDisease-associated lociGenetic variantsCausal genetic variantsDisease-associated variantsComplex traitsGenetic variationRegulatory regionsGenomic featuresCausal variantsRegulatory potentialAssociation studiesReporter activityDisease-associated haplotypeLinkage disequilibriumCommon variantsTight linkage disequilibriumExperimental assaysCell linesImmune cell linesLociAccessible regionsTNFAIP3TNFAIP3 locus