2022
Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk
Yin X, Bose D, Kwon A, Hanks S, Jackson A, Stringham H, Welch R, Oravilahti A, Silva L, FinnGen, Locke A, Fuchsberger C, Service S, Erdos M, Bonnycastle L, Kuusisto J, Stitziel N, Hall I, Morrison J, Ripatti S, Palotie A, Freimer N, Collins F, Mohlke K, Scott L, Fauman E, Burant C, Boehnke M, Laakso M, Wen X. Integrating transcriptomics, metabolomics, and GWAS helps reveal molecular mechanisms for metabolite levels and disease risk. American Journal Of Human Genetics 2022, 109: 1727-1741. PMID: 36055244, PMCID: PMC9606383, DOI: 10.1016/j.ajhg.2022.08.007.Peer-Reviewed Original ResearchConceptsGenome-wide association studiesMolecular mechanismsGWAS resultsDisease traitsGene expressionMetabolic pathwaysTranscriptome-wide associationSame causal variantsMetabolomics resultsTranscriptomic resultsMolecular traitsTranscriptomic dataGTEx projectCausal variantsGlycerophospholipid metabolic pathwayTranscriptomicsAssociation studiesColocalization analysisMetabolite levelsDistinct pathwaysPutative causal effectGenetic variantsGenesUGT1A4 expressionGenetic association
2020
Mapping and characterization of structural variation in 17,795 human genomes
Abel HJ, Larson DE, Regier AA, Chiang C, Das I, Kanchi KL, Layer RM, Neale BM, Salerno WJ, Reeves C, Buyske S, Matise T, Muzny D, Zody M, Lander E, Dutcher S, Stitziel N, Hall I. Mapping and characterization of structural variation in 17,795 human genomes. Nature 2020, 583: 83-89. PMID: 32460305, PMCID: PMC7547914, DOI: 10.1038/s41586-020-2371-0.Peer-Reviewed Original ResearchConceptsStructural variantsWhole-genome sequencingHuman genomeUltra-rare structural variantsRare structural variantsSuch structural variantsSingle nucleotide variantsNoncoding elementsDosage sensitivityGenomeHuman geneticsSmall insertionsComplex rearrangementsDeletion variantsSmall variantsStructural variationsGenesSequencingAllelesForm of variationVariantsElement classesSite frequency dataDeleterious effectsGenetics
2017
Landscape of X chromosome inactivation across human tissues
Aguet F, Ardlie K, Cummings B, Gelfand E, Getz G, Hadley K, Handsaker R, Huang K, Kashin S, Karczewski K, Lek M, Li X, MacArthur D, Nedzel J, Nguyen D, Noble M, Segrè A, Trowbridge C, Tukiainen T, Abell N, Balliu B, Barshir R, Basha O, Battle A, Bogu G, Brown A, Brown C, Castel S, Chen L, Chiang C, Conrad D, Cox N, Damani F, Davis J, Delaneau O, Dermitzakis E, Engelhardt B, Eskin E, Ferreira P, Frésard L, Gamazon E, Garrido-Martín D, Gewirtz A, Gliner G, Gloudemans M, Guigo R, Hall I, Han B, He Y, Hormozdiari F, Howald C, Kyung Im H, Jo B, Yong Kang E, Kim Y, Kim-Hellmuth S, Lappalainen T, Li G, Li X, Liu B, Mangul S, McCarthy M, McDowell I, Mohammadi P, Monlong J, Montgomery S, Muñoz-Aguirre M, Ndungu A, Nicolae D, Nobel A, Oliva M, Ongen H, Palowitch J, Panousis N, Papasaikas P, Park Y, Parsana P, Payne A, Peterson C, Quan J, Reverter F, Sabatti C, Saha A, Sammeth M, Scott A, Shabalin A, Sodaei R, Stephens M, Stranger B, Strober B, Sul J, Tsang E, Urbut S, van de Bunt M, Wang G, Wen X, Wright F, Xi H, Yeger-Lotem E, Zappala Z, Zaugg J, Zhou Y, Akey J, Bates D, Chan J, Chen L, Claussnitzer M, Demanelis K, Diegel M, Doherty J, Feinberg A, Fernando M, Halow J, Hansen K, Haugen E, Hickey P, Hou L, Jasmine F, Jian R, Jiang L, Johnson A, Kaul R, Kellis M, Kibriya M, Lee K, Li J, Li Q, Li X, Lin J, Lin S, Linder S, Linke C, Liu Y, Maurano M, Molinie B, Montgomery S, Nelson J, Neri F, Oliva M, Park Y, Pierce B, Rinaldi N, Rizzardi L, Sandstrom R, Skol A, Smith K, Snyder M, Stamatoyannopoulos J, Stranger B, Tang H, Tsang E, Wang L, Wang M, Van Wittenberghe N, Wu F, Zhang R, Nierras C, Branton P, Carithers L, Guan P, Moore H, Rao A, Vaught J, Gould S, Lockart N, Martin C, Struewing J, Volpi S, Addington A, Koester S, Little A, Brigham L, Hasz R, Hunter M, Johns C, Johnson M, Kopen G, Leinweber W, Lonsdale J, McDonald A, Mestichelli B, Myer K, Roe B, Salvatore M, Shad S, Thomas J, Walters G, Washington M, Wheeler J, Bridge J, Foster B, Gillard B, Karasik E, Kumar R, Miklos M, Moser M, Jewell S, Montroy R, Rohrer D, Valley D, Davis D, Mash D, Undale A, Smith A, Tabor D, Roche N, McLean J, Vatanian N, Robinson K, Sobin L, Barcus M, Valentino K, Qi L, Hunter S, Hariharan P, Singh S, Um K, Matose T, Tomaszewski M, Barker L, Mosavel M, Siminoff L, Traino H, Flicek P, Juettemann T, Ruffier M, Sheppard D, Taylor K, Trevanion S, Zerbino D, Craft B, Goldman M, Haeussler M, Kent W, Lee C, Paten B, Rosenbloom K, Vivian J, Zhu J. Landscape of X chromosome inactivation across human tissues. Nature 2017, 550: 244-248. PMID: 29022598, PMCID: PMC5685192, DOI: 10.1038/nature24265.Peer-Reviewed Original ResearchGenetic effects on gene expression across human tissues
Aguet F, Brown A, Castel S, Davis J, He Y, Jo B, Mohammadi P, Park Y, Parsana P, Segrè A, Strober B, Zappala Z, Cummings B, Gelfand E, Hadley K, Huang K, Lek M, Li X, Nedzel J, Nguyen D, Noble M, Sullivan T, Tukiainen T, MacArthur D, Getz G, Addington A, Guan P, Koester S, Little A, Lockhart N, Moore H, Rao A, Struewing J, Volpi S, Brigham L, Hasz R, Hunter M, Johns C, Johnson M, Kopen G, Leinweber W, Lonsdale J, McDonald A, Mestichelli B, Myer K, Roe B, Salvatore M, Shad S, Thomas J, Walters G, Washington M, Wheeler J, Bridge J, Foster B, Gillard B, Karasik E, Kumar R, Miklos M, Moser M, Jewell S, Montroy R, Rohrer D, Valley D, Mash D, Davis D, Sobin L, Barcus M, Branton P, Abell N, Balliu B, Delaneau O, Frésard L, Gamazon E, Garrido-Martín D, Gewirtz A, Gliner G, Gloudemans M, Han B, He A, Hormozdiari F, Li X, Liu B, Kang E, McDowell I, Ongen H, Palowitch J, Peterson C, Quon G, Ripke S, Saha A, Shabalin A, Shimko T, Sul J, Teran N, Tsang E, Zhang H, Zhou Y, Bustamante C, Cox N, Guigó R, Kellis M, McCarthy M, Conrad D, Eskin E, Li G, Nobel A, Sabatti C, Stranger B, Wen X, Wright F, Ardlie K, Dermitzakis E, Lappalainen T, Aguet F, Ardlie K, Cummings B, Gelfand E, Getz G, Hadley K, Handsaker R, Huang K, Kashin S, Karczewski K, Lek M, Li X, MacArthur D, Nedzel J, Nguyen D, Noble M, Segrè A, Trowbridge C, Tukiainen T, Abell N, Balliu B, Barshir R, Basha O, Battle A, Bogu G, Brown A, Brown C, Castel S, Chen L, Chiang C, Conrad D, Cox N, Damani F, Davis J, Delaneau O, Dermitzakis E, Engelhardt B, Eskin E, Ferreira P, Frésard L, Gamazon E, Garrido-Martín D, Gewirtz A, Gliner G, Gloudemans M, Guigo R, Hall I, Han B, He Y, Hormozdiari F, Howald C, Kyung Im H, Jo B, Yong Kang E, Kim Y, Kim-Hellmuth S, Lappalainen T, Li G, Li X, Liu B, Mangul S, McCarthy M, McDowell I, Mohammadi P, Monlong J, Montgomery S, Muñoz-Aguirre M, Ndungu A, Nicolae D, Nobel A, Oliva M, Ongen H, Palowitch J, Panousis N, Papasaikas P, Park Y, Parsana P, Payne A, Peterson C, Quan J, Reverter F, Sabatti C, Saha A, Sammeth M, Scott A, Shabalin A, Sodaei R, Stephens M, Stranger B, Strober B, Sul J, Tsang E, Urbut S, van de Bunt M, Wang G, Wen X, Wright F, Xi H, Yeger-Lotem E, Zappala Z, Zaugg J, Zhou Y, Akey J, Bates D, Chan J, Chen L, Claussnitzer M, Demanelis K, Diegel M, Doherty J, Feinberg A, Fernando M, Halow J, Hansen K, Haugen E, Hickey P, Hou L, Jasmine F, Jian R, Jiang L, Johnson A, Kaul R, Kellis M, Kibriya M, Lee K, Billy Li J, Li Q, Li X, Lin J, Lin S, Linder S, Linke C, Liu Y, Maurano M, Molinie B, Montgomery S, Nelson J, Neri F, Oliva M, Park Y, Pierce B, Rinaldi N, Rizzardi L, Sandstrom R, Skol A, Smith K, Snyder M, Stamatoyannopoulos J, Stranger B, Tang H, Tsang E, Wang L, Wang M, Van Wittenberghe N, Wu F, Zhang R, Nierras C, Branton P, Carithers L, Guan P, Moore H, Rao A, Vaught J, Gould S, Lockart N, Martin C, Struewing J, Volpi S, Addington A, Koester S, Little A, Brigham L, Hasz R, Hunter M, Johns C, Johnson M, Kopen G, Leinweber W, Lonsdale J, McDonald A, Mestichelli B, Myer K, Roe B, Salvatore M, Shad S, Thomas J, Walters G, Washington M, Wheeler J, Bridge J, Foster B, Gillard B, Karasik E, Kumar R, Miklos M, Moser M, Jewell S, Montroy R, Rohrer D, Valley D, Davis D, Mash D, Undale A, Smith A, Tabor D, Roche N, McLean J, Vatanian N, Robinson K, Sobin L, Barcus M, Valentino K, Qi L, Hunter S, Hariharan P, Singh S, Um K, Matose T, Tomaszewski M, Barker L, Mosavel M, Siminoff L, Traino H, Flicek P, Juettemann T, Ruffier M, Sheppard D, Taylor K, Trevanion S, Zerbino D, Craft B, Goldman M, Haeussler M, Kent W, Lee C, Paten B, Rosenbloom K, Vivian J, Zhu J. Genetic effects on gene expression across human tissues. Nature 2017, 550: 204-213. PMID: 29022597, PMCID: PMC5776756, DOI: 10.1038/nature24277.Peer-Reviewed Original ResearchConceptsGene expression levelsGenetic effectsExpression levelsGenotype-Tissue Expression (GTEx) projectLocal genetic variationMajority of genesHuman genetic traitsDisease-associated variationMolecular functionsGene regulationHuman genomeHuman tissuesExpression projectGenetic variationGenetic basisDiverse tissuesGene expressionTissue specificityGenetic traitsCellular mechanismsGenesFunctional propertiesGenomeTissueLoci