Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

American Journal of Human Genetics

Volumn 102, Issue 6, 2018, Pages 1185-1194

  Ni, Guiyan ^a,b   Moser, Gerhard ^a,b   Ripke, Stephan ^d   Neale, Benjamin M ^d   Corvin, Aiden ^d   Walters, James T R ^d   Farh, Kai How ^d   Holmans, Peter A ^d   Lee, Phil ^d   Bulik Sullivan, Brendan ^d   Collier, David A ^d   Huang, Hailiang ^d   Pers, Tune H ^d   Agartz, Ingrid ^d   Agerbo, Esben ^d   Albus, Margot ^d   Alexander, Madeline ^d   Amin, Farooq ^d   Bacanu, Silviu A ^d   Begemann, Martin ^d   Belliveau, Richard A ^d   Bene, Judit ^d   Bergen, Sarah E ^d   Bevilacqua, Elizabeth ^d   Bigdeli, Tim B ^d   Black, Donald W ^d   Bruggeman, Richard ^d   Buccola, Nancy G ^d   Buckner, Randy L ^d   Byerley, William ^d   Cahn, Wiepke ^d   Cai, Guiqing ^d   Campion, Dominique ^d   Cantor, Rita M ^d   Carr, Vaughan J ^d   Carrera, Noa ^d   Catts, Stanley V ^d   Chambert, Kimberly D ^d   Chan, Raymond C K ^d   Chen, Ronald Y L ^d   Chen, Eric Y H ^d   Cheng, Wei ^d   Cheung, Eric F C ^d   Chong, Siow Ann ^d   Cloninger, C Robert ^d   Cohen, David ^d   Cohen, Nadine ^d   Cormican, Paul ^d   Craddock, Nick ^d   Crowley, James J ^d   Curtis, David ^d   Davidson, Michael ^d   Davis, Kenneth L ^d   Degenhardt, Franziska ^d   Del Favero, Jurgen ^d   Demontis, Ditte ^d   Dikeos, Dimitris ^d   Dinan, Timothy ^d   Djurovic, Srdjan ^d   Donohoe, Gary ^d   Drapeau, Elodie ^d   Duan, Jubao ^d   Dudbridge, Frank ^d   Durmishi, Naser ^d   Eichhammer, Peter ^d   Eriksson, Johan ^d   Escott Price, Valentina ^d   Essioux, Laurent ^d   Fanous, Ayman H ^d   Farrell, Martilias S ^d   Frank, Josef ^d   Franke, Lude ^d   Freedman, Robert ^d   Freimer, Nelson B ^d   Friedl, Marion ^d   Friedman, Joseph I ^d   Fromer, Menachem ^d   Genovese, Giulio ^d   Georgieva, Lyudmila ^d   Giegling, Ina ^d   Giusti Rodríguez, Paola ^d   Godard, Stephanie ^d   Goldstein, Jacqueline I ^d   Golimbet, Vera ^d   Gopal, Srihari ^d   Gratten, Jacob ^d   de Haan, Lieuwe ^d   Hammer, Christian ^d   Hamshere, Marian L ^d   Hansen, Mark ^d   Hansen, Thomas ^d   Haroutunian, Vahram ^d   Hartmann, Annette M ^d   Henskens, Frans A ^d   Herms, Stefan ^d   Hirschhorn, Joel N ^d   Hoffmann, Per ^d   Hofman, Andrea ^d   Hollegaard, Mads V ^d   Hougaard, David M ^d   Ikeda, Masashi ^d   Joa, Inge ^d   Juliá, Antonio ^d   Kahn, René S ^d   Kalaydjieva, Luba ^d   Karachanak Yankova, Sena ^d   Karjalainen, Juha ^d   Kavanagh, David ^d   Keller, Matthew C ^d   Kennedy, James L ^d   Khrunin, Andrey ^d   Kim, Yunjung ^d   Klovins, Janis ^d   Knowles, James A ^d   Konte, Bettina ^d   Kucinskas, Vaidutis ^d   Kucinskiene, Zita Ausrele ^d   Kuzelova Ptackova, Hana ^d   Kähler, Anna K ^d   Laurent, Claudine ^d   Keong, Jimmy Lee Chee ^d   Legge, Sophie E ^d   Lerer, Bernard ^d   Li, Miaoxin ^d   Li, Tao ^d   Liang, Kung Yee ^d   Lieberman, Jeffrey ^d   Limborska, Svetlana ^d   Loughland, Carmel M ^d   Lubinski, Jan ^d   Lönnqvist, Jouko ^d   Macek, Milan ^d   Magnusson, Patrik K E ^d   Maher, Brion S ^d   Maier, Wolfgang ^d   Mallet, Jacques ^d   Marsal, Sara ^d   Mattheisen, Manuel ^d   Mattingsda, Morten ^d   McCarley, Robert W ^d   McDonald, Colm ^d   McIntosh, Andrew M ^d   Meier, Sandra ^d   Meijer, Carin J ^d   Melegh, Bela ^d   Melle, Ingrid ^d   Mesholam Gately, Raquelle I ^d   Metspalu, Andres ^d   Michie, Patricia T ^d   Milani, Lili ^d   Milanova, Vihra ^d   Mokrab, Younes ^d   Morris, Derek W ^d   Mors, Ole ^d   Murphy, Kieran C ^d   Murray, Robin M ^d   Myin Germeys, Inez ^d   Müller Myhsok, Bertram ^d   Nelis, Mari ^d   Nenadic, Igor ^d   Nertney, Deborah A ^d   Nestadt, Gerald ^d   Nicodemus, Kristin K ^d   Nikitina Zake, Liene ^d   Nisenbaum, Laura ^d   Nordin, Annelie ^d   O'Callaghan, Eadbhard ^d   O'Dushlaine, Colm ^d   O'Neill, F Anthony ^d   Oh, Sang Yun ^d   Olinc, Ann ^d   Olsen, Line ^d   Van Os, Jim ^d   Pantelis, Christos ^d   Papadimitriou, George N ^d   Papio, Sergi ^d   Parkhomenko, Elena ^d   Pato, Michele T ^d   Paunio, Tiina ^d   Pejovic Milovancevic, Milica ^d   Perkins, Diana O ^d   Pietiläinenl, Olli ^d   Pimm, Jonathan ^d   Pocklington, Andrew J ^d   Powell, John ^d   Price, Alkes ^d   Pulver, Ann E ^d   Purcell, Shaun M ^d   Quested, Digby ^d   Rasmussen, Henrik B ^d   Reichenberg, Abraham ^d   Reimers, Mark A ^d   Richards, Alexander L ^d   Roffman, Joshua L ^d   Roussos, Panos ^d   Ruderfer, Douglas M ^d   Salomaa, Veikko ^d   Sanders, Alan R ^d   Schall, Ulrich ^d   Schubert, Christian R ^d   Schulze, Thomas G ^d   Schwab, Sibylle G ^d   Scolnick, Edward M ^d   Scott, Rodney J ^d   Seidman, Larry J ^d   Shi, Jianxin ^d   Sigurdsson, Engilbert ^d   Silagadze, Teimuraz ^d   Silverman, Jeremy M ^d   Sim, Kang ^d   Slominsky, Petr ^d   Smoller, Jordan W ^d   So, Hon Cheong ^d   Spencer, Chris C A ^d   Stah, Eli A ^d   Stefansson, Hreinn ^d   Steinberg, Stacy ^d   Stogmann, Elisabeth ^d   Straub, Richard E ^d   Strengman, Eric ^d   Strohmaier, Jana ^d   Stroup, T Scott ^d   Subramaniam, Mythily ^d   Suvisaari, Jaana ^d   Svrakic, Dragan M ^d   Szatkiewicz, Jin P ^d   Söderman, Erik ^d   Thirumalai, Srinivas ^d   Toncheva, Draga ^d   Tosato, Sarah ^d   Veijola, Juha ^d   Waddington, John ^d   Walsh, Dermot ^d   Wang, Dai ^d   Wang, Qiang ^d   Webb, Bradley T ^d   Weiser, Mark ^d   Wildenauer, Dieter B ^d   Williams, Nigel M ^d   Williams, Stephanie ^d   Witt, Stephanie H ^d   Wolen, Aaron R ^d   Wong, Emily H M ^d   Wormley, Brandon K ^d   Xi, Hualin Simon ^d   Zai, Clement C ^d   Zheng, Xuebin ^d   Zimprich, Fritz ^d   Stefansson, Kari ^d   Visscher, Peter M ^d   Adolfsson, Rolf ^d   Andreassen, Ole A ^d   Blackwood, Douglas H R ^d   Bramon, Elvira ^d   Buxbaum, Joseph D ^d   Børglum, Anders D ^d   Cichon, Sven ^d   Darvasi, Ariel ^d   Domenici, Enrico ^d   Ehrenreich, Hannelore ^d   Esko, Tõnu ^d   Gejman, Pablo V ^d   Gill, Michael ^d   Gurling, Hugh ^d   Hultman, Christina M ^d   Iwata, Nakao ^d   Jablensky, Assen V ^d   Jönsson, Erik G ^d   Kendler, Kenneth S ^d   Kirov, George ^d   Knight, Jo ^d   Lencz, Todd ^d   Levinson, Douglas F ^d   Li, Qingqin S ^d   Liu, Jianjun ^d   Malhotra, Anil K ^d   McCarrol, Steven A ^d   McQuillin, Andrew ^d   Moran, Jennifer L ^d   Mortensen, Preben B ^d   Mowry, Bryan J ^d   Nöthen, Markus M ^d   Ophoff, Roel A ^d   Owen, Michael J ^d   Palotie, Aarno ^d   Pato, Carlos N ^d   Petryshen, Tracey L ^d   Posthuma, Danielle ^d   Rietsche, Marcella ^d   Riley, Brien P ^d   Rujescu, Dan ^d   Sham, Pak C ^d   Sklar, Pamela ^d   St Clair, David ^d   Weinberger, Daniel R ^d   Wendland, Jens R ^d   Werge, Thomas ^d   Daly, Mark J ^d   Sullivan, Patrick F ^d   O'Donovan, Michael C ^d   Wray, Naomi R ^c   Lee, S Hong ^a,b,c   more..

^a UNIVERSITY OF SOUTH AUSTRALIA   (Australia)

^b UNIVERSITY OF NEW ENGLAND   (Australia)

^c UNIVERSITY OF QUEENSLAND   (Australia)

^d NONE

Author keywords

accuracy; biasedness; body mass index; genetic correlation; genome wide SNPs; genomic restricted maximum likelihood; height; linkage disequilibrium score regression; schizophrenia; SNP heritability

Indexed keywords

ARTICLE; BODY MASS; CORRELATION ANALYSIS; ENRICHMENT CULTURE; ETHNICITY; GENE LINKAGE DISEQUILIBRIUM; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOMICS; GENOTYPE; HUMAN; INTERGENERIC HYBRIDIZATION; INTRON; PRIORITY JOURNAL; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM; ADULT; BODY HEIGHT; COMPUTER SIMULATION; GENETIC DATABASE; GENETICS; HAPLOTYPE; HUMAN GENOME; INHERITANCE; PHENOTYPE; REGRESSION ANALYSIS; STATISTICAL MODEL;

ADULT; BODY HEIGHT; COMPUTER SIMULATION; DATABASES, GENETIC; GENOME, HUMAN; GENOTYPE; HAPLOTYPES; HUMANS; INHERITANCE PATTERNS; LIKELIHOOD FUNCTIONS; LINKAGE DISEQUILIBRIUM; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; REGRESSION ANALYSIS; SCHIZOPHRENIA;

EID: 85046126170     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2018.03.021     Document Type: Article

References (37)

1. Mehta, D., Tropf, F.C., Gratten, J., Bakshi, A., Zhu, Z., Bacanu, S.-A., Hemani, G., Magnusson, P.K.E., Barban, N., Esko, T., et al., Schizophrenia Working Group of the Psychiatric Genomics Consortium, LifeLines Cohort Study, and TwinsUK. Evidence for genetic overlap between schizophrenia and age at first birth in women. JAMA Psychiatry 73 (2016), 497–505.
2. Lee, S.H., Byrne, E.M., Hultman, C.M., Kähler, A., Vinkhuyzen, A.A.E., Ripke, S., Andreassen, O.A., Frisell, T., Gusev, A., Hu, X., et al. Schizophrenia Working Group of the Psychiatric Genomics Consortium and Rheumatoid Arthritis Consortium International Schizophrenia Working Group of the Psychiatric Genomics Consortium Authors Schizophrenia Working Group of the Psychiatric Genomics Consortium Collaborators Rheumatoid Arthritis Consortium International Authors, Rheumatoid Arthritis Consortium International Collaborators. New data and an old puzzle: the negative association between schizophrenia and rheumatoid arthritis. Int. J. Epidemiol. 44 (2015), 1706–1721.
3. Lee, S.H., DeCandia, T.R., Ripke, S., Yang, J., Sullivan, P.F., Goddard, M.E., Keller, M.C., Visscher, P.M., Wray, N.R. Schizophrenia Psychiatric Genome-Wide Association Study Consortium (PGC-SCZ) International Schizophrenia Consortium (ISC), Molecular Genetics of Schizophrenia Collaboration (MGS). Estimating the proportion of variation in susceptibility to schizophrenia captured by common SNPs. Nat. Genet. 44 (2012), 247–250.
4. Lee, S.H., Yang, J., Goddard, M.E., Visscher, P.M., Wray, N.R., Estimation of pleiotropy between complex diseases using single-nucleotide polymorphism-derived genomic relationships and restricted maximum likelihood. Bioinformatics 28 (2012), 2540–2542.
5. Harville, D.A., Maximum likelihood approaches to variance component estimation and to related problems. J. Am. Stat. Assoc. 72 (1977), 320–338.
6. Patterson, H.D., Thompson, R., Recovery of inter-block information when block sizes are unequal. Biometrika 58 (1971), 545–554.
7. Neale, M., Cardon, L., Methodology for Genetic Studies of Twins and Families. 2013, Springer Science & Business Media.
8. VanRaden, P.M., Efficient methods to compute genomic predictions. J. Dairy Sci. 91 (2008), 4414–4423.
9. Yang, J., Lee, S.H., Goddard, M.E., Visscher, P.M., GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88 (2011), 76–82.
10. Bulik-Sullivan, B.K., Loh, P.R., Finucane, H.K., Ripke, S., Yang, J., Patterson, N., Daly, M.J., Price, A.L., Neale, B.M., Schizophrenia Working Group of the Psychiatric Genomics Consortium. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47 (2015), 291–295.
11. Bulik-Sullivan, B., Finucane, H.K., Anttila, V., Gusev, A., Day, F.R., Loh, P.R., Duncan, L., Perry, J.R., Patterson, N., Robinson, E.B., et al. ReproGen Consortium Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47 (2015), 1236–1241.
12. Zheng, J., Erzurumluoglu, A.M., Elsworth, B.L., Kemp, J.P., Howe, L., Haycock, P.C., Hemani, G., Tansey, K., Laurin, C., Pourcain, B.S., et al., Early Genetics and Lifecourse Epidemiology (EAGLE) Eczema Consortium. LD Hub: a centralized database and web interface to perform LD score regression that maximizes the potential of summary level GWAS data for SNP heritability and genetic correlation analysis. Bioinformatics 33 (2017), 272–279.
13. Finucane, H.K., Bulik-Sullivan, B., Gusev, A., Trynka, G., Reshef, Y., Loh, P.R., Anttila, V., Xu, H., Zang, C., Farh, K., et al. ReproGen Consortium Schizophrenia Working Group of the Psychiatric Genomics Consortium, RACI Consortium. Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat. Genet. 47 (2015), 1228–1235.
14. Lee, S.H., van der Werf, J.H., MTG2: an efficient algorithm for multivariate linear mixed model analysis based on genomic information. Bioinformatics 32 (2016), 1420–1422.
15. Maier, R., Moser, G., Chen, G.-B., Ripke, S., Coryell, W., Potash, J.B., Scheftner, W.A., Shi, J., Weissman, M.M., Hultman, C.M., et al., Cross-Disorder Working Group of the Psychiatric Genomics Consortium. Joint analysis of psychiatric disorders increases accuracy of risk prediction for schizophrenia, bipolar disorder, and major depressive disorder. Am. J. Hum. Genet. 96 (2015), 283–294.
16. Collins, R., What makes UK Biobank special?. Lancet 379 (2012), 1173–1174.
17. Lynch, M., Walsh, B., Genetics and Analysis of Quantitative Traits. 1998, Sinauer Sunderland, MA.
18. Sawcer, S., Hellenthal, G., Pirinen, M., Spencer, C.C., Patsopoulos, N.A., Moutsianas, L., Dilthey, A., Su, Z., Freeman, C., Hunt, S.E., et al. International Multiple Sclerosis Genetics Consortium, Wellcome Trust Case Control Consortium 2. Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature 476 (2011), 214–219.
19. Mells, G.F., Floyd, J.A.B., Morley, K.I., Cordell, H.J., Franklin, C.S., Shin, S.-Y., Heneghan, M.A., Neuberger, J.M., Donaldson, P.T., Day, D.B., et al. UK PBC Consortium, Wellcome Trust Case Control Consortium 3. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat. Genet. 43 (2011), 329–332.
20. Bellenguez, C., Bevan, S., Gschwendtner, A., Spencer, C.C., Burgess, A.I., Pirinen, M., Jackson, C.A., Traylor, M., Strange, A., Su, Z., et al. International Stroke Genetics Consortium (ISGC), Wellcome Trust Case Control Consortium 2 (WTCCC2). Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke. Nat. Genet. 44 (2012), 328–333.
21. Tsoi, L.C., Spain, S.L., Knight, J., Ellinghaus, E., Stuart, P.E., Capon, F., Ding, J., Li, Y., Tejasvi, T., Gudjonsson, J.E., et al. Collaborative Association Study of Psoriasis (CASP) Genetic Analysis of Psoriasis Consortium Psoriasis Association Genetics Extension, Wellcome Trust Case Control Consortium 2. Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nat. Genet. 44 (2012), 1341–1348.
22. Banda, Y., Kvale, M.N., Hoffmann, T.J., Hesselson, S.E., Ranatunga, D., Tang, H., Sabatti, C., Croen, L.A., Dispensa, B.P., Henderson, M., et al. Characterizing race/ethnicity and genetic ancestry for 100,000 subjects in the genetic epidemiology research on adult health and aging (GERA) cohort. Genetics 200 (2015), 1285–1295.
23. Lee, S.H., Weerasinghe, W.M.S.P., Wray, N.R., Goddard, M.E., van der Werf, J.H.J., Using information of relatives in genomic prediction to apply effective stratified medicine. Sci. Rep., 7, 2017, 42091.
24. Gusev, A., Lee, S.H., Trynka, G., Finucane, H., Vilhjálmsson, B.J., Xu, H., Zang, C., Ripke, S., Bulik-Sullivan, B., Stahl, E., et al. Schizophrenia Working Group of the Psychiatric Genomics Consortium SWE-SCZ Consortium Schizophrenia Working Group of the Psychiatric Genomics Consortium, SWE-SCZ Consortium. Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases. Am. J. Hum. Genet. 95 (2014), 535–552.
25. Schizophrenia Working Group of the Psychiatric Genomics Consortium. Biological insights from 108 schizophrenia-associated genetic loci. Nature 511 (2014), 421–427.
26. Locke, A.E., Kahali, B., Berndt, S.I., Justice, A.E., Pers, T.H., Day, F.R., Powell, C., Vedantam, S., Buchkovich, M.L., Yang, J., et al. LifeLines Cohort Study ADIPOGen Consortium AGEN-BMI Working Group CARDIOGRAMplusC4D Consortium CKDGen Consortium GLGC ICBP MAGIC Investigators MuTHER Consortium MIGen Consortium PAGE Consortium ReproGen Consortium GENIE Consortium, International Endogene Consortium. Genetic studies of body mass index yield new insights for obesity biology. Nature 518 (2015), 197–206.
27. Wood, A.R., Esko, T., Yang, J., Vedantam, S., Pers, T.H., Gustafsson, S., Chu, A.Y., Estrada, K., Luan, J., Kutalik, Z., et al. Electronic Medical Records and Genomics (eMEMERGEGE) Consortium MIGen Consortium PAGEGE Consortium, LifeLines Cohort Study. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat. Genet. 46 (2014), 1173–1186.
28. Pasaniuc, B., Price, A.L., Dissecting the genetics of complex traits using summary association statistics. Nat. Rev. Genet. 18 (2017), 117–127.
29. Lee, S.H., Yang, J., Chen, G.B., Ripke, S., Stahl, E.A., Hultman, C.M., Sklar, P., Visscher, P.M., Sullivan, P.F., Goddard, M.E., Wray, N.R., Estimation of SNP heritability from dense genotype data. Am. J. Hum. Genet. 93 (2013), 1151–1155.
30. Speed, D., Hemani, G., Johnson, M.R., Balding, D.J., Improved heritability estimation from genome-wide SNPs. Am. J. Hum. Genet. 91 (2012), 1011–1021.
31. Gunnell, D., Harrison, G., Whitley, E., Lewis, G., Tynelius, P., Rasmussen, F., The association of fetal and childhood growth with risk of schizophrenia. Cohort study of 720,000 Swedish men and women. Schizophr. Res. 79 (2005), 315–322.
32. Bacanu, S.A., Chen, X., Kendler, K.S., The genetic overlap between schizophrenia and height. Schizophr. Res. 151 (2013), 226–228.
33. Speed, D., Cai, N., Johnson, M.R., Nejentsev, S., Balding, D.J., UCLEB Consortium. Reevaluation of SNP heritability in complex human traits. Nat. Genet. 49 (2017), 986–992.
34. de Los Campos, G., Vazquez, A.I., Fernando, R., Klimentidis, Y.C., Sorensen, D., Prediction of complex human traits using the genomic best linear unbiased predictor. PLoS Genet., 9, 2013 e1003608–e1003608.
35. Yang, J., Bakshi, A., Zhu, Z., Hemani, G., Vinkhuyzen, A.A.E., Lee, S.H., Robinson, M.R., Perry, J.R.B., Nolte, I.M., van Vliet-Ostaptchouk, J.V., et al., LifeLines Cohort Study. Genetic variance estimation with imputed variants finds negligible missing heritability for human height and body mass index. Nat. Genet. 47 (2015), 1114–1120.
36. Shi, H., Mancuso, N., Spendlove, S., Pasaniuc, B., Local genetic correlation gives insights into the shared genetic architecture of complex traits. Am. J. Hum. Genet. 101 (2017), 737–751.
37. Lu, Q., Li, B., Ou, D., Erlendsdottir, M., Powles, R.L., Jiang, T., Hu, Y., Chang, D., Jin, C., Dai, W., et al. A powerful approach to estimating annotation-stratified genetic covariance via GWAS summary statistics. Am. J. Hum. Genet. 101 (2017), 939–964.