Zhan J, Arking DE, Bader JS. Discovering patterns of pleiotropy in genome-wide association studies. bioRxiv. 2018;28:273540.
Google Scholar
Chesmore K, Bartlett J, Williams SM. The ubiquity of pleiotropy in human disease. Hum Genet. 2017;21:1–6.
Google Scholar
Socrates A, Bond T, Karhunen V, Auvinen J, Rietveld C, Veijola J, et al. Polygenic risk scores applied to a single cohort reveal pleiotropy among hundreds of human phenotypes. bioRxiv. 2017;14:203257.
Google Scholar
Solovieff N, Cotsapas C, Lee PH, Purcell SM, Smoller JW. Pleiotropy in complex traits: challenges and strategies. Nat Rev Genet. 2013;14(7):483–95.
Article
CAS
PubMed
PubMed Central
Google Scholar
Keightley PD, Hill WG. Variation maintained in quantitative traits with mutation–selection balance: pleiotropic side-effects on fitness traits. Proc R Soc Lond B. 1990;242(1304):95–100.
Article
Google Scholar
Paaby AB, Rockman MV. The many faces of pleiotropy. Trends Genet. 2013;29(2):66–73.
Article
CAS
PubMed
Google Scholar
Tyler AL, Asselbergs FW, Williams SM, Moore JH. Shadows of complexity: what biological networks reveal about epistasis and pleiotropy. BioEssays. 2009;31(2):220–7.
Article
PubMed
PubMed Central
Google Scholar
Pickrell JK, Berisa T, Liu JZ, Ségurel L, Tung JY, Hinds DA. Detection and interpretation of shared genetic influences on 42 human traits. Nat Genet. 2016;48(7):709–17.
Article
CAS
PubMed
PubMed Central
Google Scholar
Kanai M, Akiyama M, Takahashi A, Matoba N, Momozawa Y, Ikeda M, et al. Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases. Nat Genet. 2018;50(3):390–400.
Article
CAS
PubMed
Google Scholar
Pasaniuc B, Price AL. Dissecting the genetics of complex traits using summary association statistics. Nat Rev Genet. 2017;18(2):117–27.
Article
CAS
PubMed
Google Scholar
Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 2013;45(11):1345–52.
Article
CAS
PubMed
PubMed Central
Google Scholar
Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60(25):2631–9.
Article
CAS
PubMed
Google Scholar
Burgess S, Freitag DF, Khan H, Gorman DN, Thompson SG. Using multivariable Mendelian randomization to disentangle the causal effects of lipid fractions. PLoS One. 2014;9(10):e108891.
Article
PubMed
PubMed Central
CAS
Google Scholar
Burgess S, Bowden J, Fall T, Ingelsson E, Thompson SG. Sensitivity analyses for robust causal inference from Mendelian randomization analyses with multiple genetic variants. Epidemiology. 2017;28(1):30–42.
Article
PubMed
Google Scholar
Pierce BL, Ahsan H, Vanderweele TJ. Power and instrument strength requirements for Mendelian randomization studies using multiple genetic variants. Int J Epidemiol. 2011;40(3):740–52.
Article
PubMed
Google Scholar
Boyle EA, Li YI, Pritchard JK. An expanded view of complex traits: from polygenic to Omnigenic. Cell. 2017;169(7):1177–86.
Article
CAS
PubMed
PubMed Central
Google Scholar
Abbott L, Bryant S, Churchhouse C, Ganna A, Howrigan D, Palmer D, et al. UK Biobank. [cited 2018 Aug 8]. Available from: http://www.nealelab.is/uk-biobank
Zhou W, Nielsen JB, Fritsche LG, Dey R, Gabrielsen ME, Wolford BN, et al. Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. Nat Genet. 2018;50(9):1335–41.
Article
CAS
PubMed
PubMed Central
Google Scholar
Zhou W, Nielsen JB, Fritsche LG, Elvestad ME, Wolford BN, Lin M, et al. SAIGE [Internet]. [cited 2018 Sep 21]. Available from: https://github.com/weizhouUMICH/SAIGE#uk-biobank-gwas-results
Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Consortium SWG of the PG, et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet. 2015;47(3):291.
Article
CAS
PubMed
PubMed Central
Google Scholar
McLaren W, Gil L, Hunt SE, Riat HS, Ritchie GRS, Thormann A, et al. The Ensembl variant effect predictor. Genome Biol. 2016;17(1):122.
Article
PubMed
PubMed Central
CAS
Google Scholar
Bernstein BE, Stamatoyannopoulos JA, Costello JF, Ren B, Milosavljevic A, Meissner A, et al. The NIH Roadmap Epigenomics Mapping Consortium. Nat Biotechnol. 2010;28:1045.
Article
CAS
PubMed
PubMed Central
Google Scholar
GTEx Consortium, Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group, Statistical Methods groups—Analysis Working Group, Enhancing GTEx (eGTEx) groups, NIH Common Fund, NIH/NCI, et al. Genetic effects on gene expression across human tissues. Nature. 2017;550(7675):204–13.
Article
Google Scholar
Verbanck M, Chen C-Y, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat Genet. 2018;23:1.
Google Scholar
Shin S-Y, Fauman EB, Petersen A-K, Krumsiek J, Santos R, Huang J, et al. An atlas of genetic influences on human blood metabolites. Nat Genet. 2014;46(6):543–50.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wang Z, Liao B-Y, Zhang J. Genomic patterns of pleiotropy and the evolution of complexity. PNAS. 2010;107(42):18034–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Sivakumaran S, Agakov F, Theodoratou E, Prendergast JG, Zgaga L, Manolio T, et al. Abundant pleiotropy in human complex diseases and traits. Am J Hum Genet. 2011;89(5):607–18.
Article
CAS
PubMed
PubMed Central
Google Scholar
Bowden J, Del Greco MF, Minelli C, Davey Smith G, Sheehan N, Thompson J. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017;36(11):1783–802.
Article
PubMed
PubMed Central
Google Scholar
Bowden J, Smith GD, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression. Int J Epidemiol. 2015;44(2):512–25.
Article
PubMed
PubMed Central
Google Scholar
Liu X, Li YI, Pritchard JK. Trans effects on gene expression can drive omnigenic inheritance. bioRxiv. 2018;1:425108.
Google Scholar
Prokopenko I, Poon W, Mägi R, Prasad BR, Salehi SA, Almgren P, et al. A central role for GRB10 in regulation of islet function in man. PLoS Genet. 2014;10(4):e1004235.
Article
PubMed
PubMed Central
CAS
Google Scholar
Bradfield JP, Taal HR, Timpson NJ, Scherag A, Lecoeur C, Warrington NM, et al. A genome-wide association meta-analysis identifies new childhood obesity loci. Nat Genet. 2012;44(5):526–31.
Article
CAS
PubMed
PubMed Central
Google Scholar
Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Ripke S, Wray NR, Lewis CM, Hamilton SP, Weissman MM, et al. A mega-analysis of genome-wide association studies for major depressive disorder. Mol Psychiatry. 2013;18(4):497–511.
Article
CAS
Google Scholar
van der Valk RJP, Kreiner-Møller E, Kooijman MN, Guxens M, Stergiakouli E, Sääf A, et al. A novel common variant in DCST2 is associated with length in early life and height in adulthood. Hum Mol Genet. 2015;24(4):1155–68.
Article
PubMed
CAS
Google Scholar
Liu JZ, van Sommeren S, Huang H, Ng SC, Alberts R, Takahashi A, et al. Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet. 2015;47(9):979–86.
Article
CAS
PubMed
PubMed Central
Google Scholar
Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature. 2014;511(7510):421–7.
Article
PubMed Central
CAS
Google Scholar
Hibar DP, Stein JL, Renteria ME, Arias-Vasquez A, Desrivières S, Jahanshad N, et al. Common genetic variants influence human subcortical brain structures. Nature. 2015;520(7546):224–9.
Article
CAS
PubMed
PubMed Central
Google Scholar
Taal HR, St Pourcain B, Thiering E, Das S, Mook-Kanamori DO, Warrington NM, et al. Common variants at 12q15 and 12q24 are associated with infant head circumference. Nat Genet. 2012;44(5):532–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Wood AR, Esko T, Yang J, Vedantam S, Pers TH, Gustafsson S, et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet. 2014;46(11):1173–86.
Article
CAS
PubMed
PubMed Central
Google Scholar
Global Lipids Genetics Consortium, Willer CJ, Schmidt EM, Sengupta S, Peloso GM, Gustafsson S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013;45(11):1274–83.
Article
CAS
Google Scholar
Pattaro C, Teumer A, Gorski M, Chu AY, Li M, Mijatovic V, et al. Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function. Nat Commun. 2016;7:10023.
Article
CAS
PubMed
PubMed Central
Google Scholar
Locke AE, Kahali B, Berndt SI, Justice AE, Pers TH, Day FR, et al. Genetic studies of body mass index yield new insights for obesity biology. Nature. 2015;518(7538):197–206.
Article
CAS
PubMed
PubMed Central
Google Scholar
International Consortium for Blood Pressure Genome-Wide Association Studies, Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature. 2011;478(7367):103–9.
Article
CAS
Google Scholar
Köttgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, Hundertmark C, et al. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013;45(2):145–54.
Article
PubMed
CAS
Google Scholar
Felix JF, Bradfield JP, Monnereau C, van der Valk RJP, Stergiakouli E, Chesi A, et al. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index. Hum Mol Genet. 2016;25(2):389–403.
Article
CAS
PubMed
Google Scholar
Cousminer DL, Berry DJ, Timpson NJ, Ang W, Thiering E, Byrne EM, et al. Genome-wide association and longitudinal analyses reveal genetic loci linking pubertal height growth, pubertal timing and childhood adiposity. Hum Mol Genet. 2013;22(13):2735–47.
Article
CAS
PubMed
PubMed Central
Google Scholar
Horikoshi M, Beaumont RN, Day FR, Warrington NM, Kooijman MN, Fernandez-Tajes J, et al. Genome-wide associations for birth weight and correlations with adult disease. Nature. 2016;538(7624):248–52.
Article
CAS
PubMed
PubMed Central
Google Scholar
Okbay A, Beauchamp JP, Fontana MA, Lee JJ, Pers TH, Rietveld CA, et al. Genome-wide association study identifies 74 loci associated with educational attainment. Nature. 2016;533(7604):539–42.
Article
CAS
PubMed
PubMed Central
Google Scholar
Okada Y, Wu D, Trynka G, Raj T, Terao C, Ikari K, et al. Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature. 2014;506(7488):376–81.
Article
CAS
PubMed
Google Scholar
Cousminer DL, Stergiakouli E, Berry DJ, Ang W, Groen-Blokhuis MM, Körner A, et al. Genome-wide association study of sexual maturation in males and females highlights a role for body mass and menarche loci in male puberty. Hum Mol Genet. 2014;23(16):4452–64.
Article
CAS
PubMed
PubMed Central
Google Scholar
Tobacco and Genetics Consortium. Genome-wide meta-analyses identify multiple loci associated with smoking behavior. Nat Genet. 2010;42(5):441–7.
Article
CAS
Google Scholar
Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet. 2013;381(9875):1371–9.
Article
PubMed Central
CAS
Google Scholar
Scott RA, Lagou V, Welch RP, Wheeler E, Montasser ME, Luan J, et al. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat Genet. 2012;44(9):991–1005.
Article
CAS
PubMed
PubMed Central
Google Scholar
Manning AK, LaValley M, Liu C-T, Rice K, An P, Liu Y, et al. Meta-analysis of gene-environment interaction: joint estimation of SNP and SNP×environment regression coefficients. Genet Epidemiol. 2011;35(1):11–8.
Article
PubMed
PubMed Central
Google Scholar
the CARDIoGRAMplusC4D Consortium. A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet. 2015;47(10):1121–30.
Article
CAS
Google Scholar
Morris AP, Voight BF, Teslovich TM, Ferreira T, Segrè AV, Steinthorsdottir V, et al. Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes. Nat Genet. 2012;44(9):981–90.
Article
CAS
PubMed
PubMed Central
Google Scholar
Psychiatric GWAS Consortium Bipolar Disorder Working Group. Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nat Genet. 2011;43(10):977–83.
Article
CAS
Google Scholar
Stolk L, Perry JRB, Chasman DI, He C, Mangino M, Sulem P, et al. Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways. Nat Genet. 2012;44(3):260–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Lambert JC, Ibrahim-Verbaas CA, Harold D, Naj AC, Sims R, Bellenguez C, et al. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Nat Genet. 2013;45(12):1452–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dehghan A, Dupuis J, Barbalic M, Bis JC, Eiriksdottir G, Lu C, et al. Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels. Circulation. 2011;123(7):731–8.
Article
CAS
PubMed
PubMed Central
Google Scholar
Neale BM, Medland SE, Ripke S, Asherson P, Franke B, Lesch K-P, et al. Meta-analysis of genome-wide association studies of attention-deficit/hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 2010;49(9):884–97.
Article
PubMed
PubMed Central
Google Scholar
Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson AU, et al. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010;42(2):105–16.
Article
CAS
PubMed
PubMed Central
Google Scholar
Shungin D, Winkler TW, Croteau-Chonka DC, Ferreira T, Locke AE, Mägi R, et al. New genetic loci link adipose and insulin biology to body fat distribution. Nature. 2015;518(7538):187–96.
Article
CAS
PubMed
PubMed Central
Google Scholar
Dastani Z, Hivert M-F, Timpson N, Perry JRB, Yuan X, Scott RA, et al. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012;8(3):e1002607.
Article
CAS
PubMed
PubMed Central
Google Scholar
Perry JRB, Day F, Elks CE, Sulem P, Thompson DJ, Ferreira T, et al. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche. Nature. 2014;514(7520):92–7.
Article
CAS
PubMed
PubMed Central
Google Scholar
van der Harst P, Zhang W, Mateo Leach I, Rendon A, Verweij N, Sehmi J, et al. Seventy-five genetic loci influencing the human red blood cell. Nature. 2012;492(7429):369–75.
Article
PubMed
PubMed Central
CAS
Google Scholar
Dickinson ME, Flenniken AM, Ji X, Teboul L, Wong MD, White JK, et al. High-throughput discovery of novel developmental phenotypes. Nature. 2016;537(7621):508–14.
Article
CAS
PubMed
PubMed Central
Google Scholar
Saito TL, Ohtani M, Sawai H, Sano F, Saka A, Watanabe D, et al. SCMD: Saccharomyces cerevisiae morphological database. Nucleic Acids Res. 2004;32(Database issue):D319–22.
Article
CAS
PubMed
PubMed Central
Google Scholar
Huang DW, Sherman BT, Lempicki RA. Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists. Nucleic Acids Res. 2009;37(1):1–13.
Article
CAS
Google Scholar
Huang DW, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44–57.
Article
CAS
Google Scholar
DAVID Bioinformatics Resources v.6.8. https://david.ncifcrf.gov/
Jordan DM, Verbanck M, Do R. HOPS. Github. 2019. https://github.com/rondolab/HOPS. doi:https://doi.org/10.5281/zenodo.3462163.