A systematic heritability analysis of the human whole blood transcriptome.
A systematic heritability analysis of the human whole blood transcriptome.
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DOI:
10.1007/s00439-014-1524-3
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发表时间:
2015-03
期刊:
影响因子:
5.3
通讯作者:
Levy, Daniel
中科院分区:
文献类型:
--
作者:
Huan, Tianxiao;Liu, Chunyu;Joehanes, Roby;Zhang, Xiaoling;Chen, Brian H.;Johnson, Andrew D.;Yao, Chen;Courchesne, Paul;O'Donnell, Christopher J.;Munson, Peter J.;Levy, Daniel
Genome-wide expression quantitative trait locus (eQTL) mapping may reveal common genetic variants regulating gene expression. In addition to mapping eQTLs, we systematically evaluated the heritability of the whole blood transcriptome in 5626 participants from the Framingham Heart Study. Of all gene expression measurements, about 40% exhibit evidence of being heritable (, (p<0.05]), the average heritability was estimated to be 0.13, and 10% display . In order to identify the role of eQTLs in promoting phenotype differences and disease susceptibility, we investigated the proportion of cis/trans eQTLs in different heritability categories and discovered that genes with higher heritability are more likely to have cis eQTLs that explain large proportions of variance in the expression of the corresponding genes. Single cis eQTLs explain 0.33–0.53 of variance in transcripts on average, whereas single trans eQTLs only explain 0.02–0.07. The top cis eQTLs tend to explain more variance in the corresponding gene when its is greater. Taking body mass index (BMI) as a case study, we cross-linked cis/trans eQTLs with both GWAS SNPs and differentially expressed genes for BMI. We discovered that BMI GWAS SNPs in 16p11.2 (e.g., rs7359397) are associated with several BMI differentially expressed genes in a cis manner (e.g. SULT1A1, SPNS1, and TUFM). These BMI signature genes explain a much larger proportion of variance in BMI than do the GWAS SNPs. Our results shed light the impact of eQTLs on the heritability of the human whole blood transcriptome and its relations to phenotype differences.
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影响因子:
30.8
作者:
通讯作者:
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影响因子:
64.8
作者:
通讯作者:
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影响因子:
9.8
作者:
Schadt EE;Molony C;Chudin E;Hao K;Yang X;Lum PY;Kasarskis A;Zhang B;Wang S;Suver C;Zhu J;Millstein J;Sieberts S;Lamb J;GuhaThakurta D;Derry J;Storey JD;Avila-Campillo I;Kruger MJ;Johnson JM;Rohl CA;van Nas A;Mehrabian M;Drake TA;Lusis AJ;Smith RC;Guengerich FP;Strom SC;Schuetz E;Rushmore TH;Ulrich R
通讯作者:
Ulrich R
影响因子:
30.8
作者:
Monda, Keri L.;Chen, Gary K.;Taylor, Kira C.;Palmer, Cameron;Edwards, Todd L.;Lange, Leslie A.;Ng, Maggie C. Y.;Adeyemo, Adebowale A.;Allison, Matthew A.;Bielak, Lawrence F.;Chen, Guanjie;Graff, Mariaelisa;Irvin, Marguerite R.;Rhie, Suhn K.;Li, Guo;Liu, Yongmei;Liu, Youfang;Lu, Yingchang;Nalls, Michael A.;Sun, Yan V.;Wojczynski, Mary K.;Yanek, Lisa R.;Aldrich, Melinda C.;Ademola, Adeyinka;Amos, Christopher I.;Bandera, Elisa V.;Bock, Cathryn H.;Britton, Angela;Broeckel, Ulrich;Cai, Quiyin;Caporaso, Neil E.;Carlson, Chris S.;Carpten, John;Casey, Graham;Chen, Wei-Min;Chen, Fang;Chen, Yii-Der I.;Chiang, Charleston W. K.;Coetzee, Gerhard A.;Demerath, Ellen;Deming-Halverson, Sandra L.;Driver, Ryan W.;Dubbert, Patricia;Feitosa, Mary F.;Feng, Ye;Freedman, Barry I.;Gillanders, Elizabeth M.;Gottesman, Omri;Guo, Xiuqing;Haritunians, Talin;Harris, Tamara;Harris, Curtis C.;Hennis, Anselm J. M.;Hernandez, Dena G.;McNeill, Lorna H.;Howard, Timothy D.;Howard, Barbara V.;Howard, Virginia J.;Johnson, Karen C.;Kang, Sun J.;Keating, Brendan J.;Kolb, Suzanne;Kuller, Lewis H.;Kutlar, Abdullah;Langefeld, Carl D.;Lettre, Guillaume;Lohman, Kurt;Lotay, Vaneet;Lyon, Helen;Manson, Joann E.;Maixner, William;Meng, Yan A.;Monroe, Kristine R.;Morhason-Bello, Imran;Murphy, Adam B.;Mychaleckyj, Josyf C.;Nadukuru, Rajiv;Nathanson, Katherine L.;Nayak, Uma;N'Diaye, Amidou;Nemesure, Barbara;Wu, Suh-Yuh;Leske, M. Cristina;Neslund-Dudas, Christine;Neuhouser, Marian;Nyante, Sarah;Ochs-Balcom, Heather;Ogunniyi, Adesola;Ogundiran, Temidayo O.;Ojengbede, Oladosu;Olopade, Olufunmilayo I.;Palmer, Julie R.;Ruiz-Narvaez, Edward A.;Palmer, Nicholette D.;Press, Michael F.;Rampersaud, Evandine;Rasmussen-Torvik, Laura J.;Rodriguez-Gil, Jorge L.;Salako, Babatunde;Schadt, Eric E.;Schwartz, Ann G.;Shriner, Daniel A.;Siscovick, David;Smith, Shad B.;Wassertheil-Smoller, Sylvia;Speliotes, Elizabeth K.;Spitz, Margaret R.;Sucheston, Lara;Taylor, Herman;Tayo, Bamidele O.;Tucker, Margaret A.;Van Den Berg, David J.;Edwards, Digna R. Velez;Wang, Zhaoming;Wiencke, John K.;Winkler, Thomas W.;Witte, John S.;Wrensch, Margaret;Wu, Xifeng;Yang, James J.;Levin, Albert M.;Young, Taylor R.;Zakai, Neil A.;Cushman, Mary;Zanetti, Krista A.;Zhao, Jing Hua;Zhao, Wei;Zheng, Yonglan;Zhou, Jie;Ziegler, Regina G.;Zmuda, Joseph M.;Fernandes, Jyotika K.;Gilkeson, Gary S.;Kamen, Diane L.;Hunt, Kelly J.;Spruill, Ida J.;Ambrosone, Christine B.;Ambs, Stefan;Arnett, Donna K.;Atwood, Larry;Becker, Diane M.;Berndt, Sonja I.;Bernstein, Leslie;Blot, William J.;Borecki, Ingrid B.;Bottinger, Erwin P.;Bowden, Donald W.;Burke, Gregory;Chanock, Stephen J.;Cooper, Richard S.;Ding, Jingzhong;Duggan, David;Evans, Michele K.;Fox, Caroline;Garvey, W. Timothy;Bradfield, Jonathan P.;Hakonarson, Hakon;Grant, Struan F. A.;Hsing, Ann;Chu, Lisa;Hu, Jennifer J.;Huo, Dezheng;Ingles, Sue A.;John, Esther M.;Jordan, Joanne M.;Kabagambe, Edmond K.;Kardia, Sharon L. R.;Kittles, Rick A.;Goodman, Phyllis J.;Klein, Eric A.;Kolonel, Laurence N.;Le Marchand, Loic;Liu, Simin;McKnight, Barbara;Millikan, Robert C.;Mosley, Thomas H.;Padhukasahasram, Badri;Williams, L. Keoki;Patel, Sanjay R.;Peters, Ulrike;Pettaway, Curtis A.;Peyser, Patricia A.;Psaty, Bruce M.;Redline, Susan;Rotimi, Charles N.;Rybicki, Benjamin A.;Sale, Michele M.;Schreiner, Pamela J.;Signorello, Lisa B.;Singleton, Andrew B.;Stanford, Janet L.;Strom, Sara S.;Thun, Michael J.;Vitolins, Mara;Zheng, Wei;Moore, Jason H.;Williams, Scott M.;Ketkar, Shamika;Zhu, Xiaofeng;Zonderman, Alan B.;Kooperberg, Charles;Papanicolaou, George J.;Henderson, Brian E.;Reiner, Alex P.;Hirschhorn, Joel N.;Loos, Ruth J. F.;North, Kari E.;Haiman, Christopher A.
通讯作者:
Haiman, Christopher A.
影响因子:
64.8
作者:
Ehret, Georg B.;Munroe, Patricia B.;Rice, Kenneth M.;Bochud, Murielle;Johnson, Andrew D.;Chasman, Daniel I.;Smith, Albert V.;Tobin, Martin D.;Verwoert, Germaine C.;Hwang, Shih-Jen;Pihur, Vasyl;Vollenweider, Peter;O'Reilly, Paul F.;Amin, Najaf;Bragg-Gresham, Jennifer L.;Teumer, Alexander;Glazer, Nicole L.;Launer, Lenore;Zhao, Jing Hua;Aulchenko, Yurii;Heath, Simon;Sober, Siim;Parsa, Afshin;Luan, Jian'an;Arora, Pankaj;Dehghan, Abbas;Zhang, Feng;Lucas, Gavin;Hicks, Andrew A.;Jackson, Anne U.;Peden, John F.;Tanaka, Toshiko;Wild, Sarah H.;Rudan, Igor;Igl, Wilmar;Milaneschi, Yuri;Parker, Alex N.;Fava, Cristiano;Chambers, John C.;Fox, Ervin R.;Kumari, Meena;Go, Min Jin;van der Harst, Pim;Kao, Wen Hong Linda;Sjogren, Marketa;Vinay, D. G.;Alexander, Myriam;Tabara, Yasuharu;Shaw-Hawkins, Sue;Whincup, Peter H.;Liu, Yongmei;Shi, Gang;Kuusisto, Johanna;Tayo, Bamidele;Seielstad, Mark;Sim, Xueling;Khanh-Dung Hoang Nguyen;Lehtimaki, Terho;Matullo, Giuseppe;Wu, Ying;Gaunt, Tom R.;Onland-Moret, N. Charlotte;Cooper, Matthew N.;Platou, Carl G. P.;Org, Elin;Hardy, Rebecca;Dahgam, Santosh;Palmen, Jutta;Vitart, Veronique;Braund, Peter S.;Kuznetsova, Tatiana;Uiterwaal, Cuno S. P. M.;Adeyemo, Adebowale;Palmas, Walter;Campbell, Harry;Ludwig, Barbara;Tomaszewski, Maciej;Tzoulaki, Ioanna;Palmer, Nicholette D.;Aspelund, Thor;Garcia, Melissa;Chang, Yen-Pei C.;O'Connell, Jeffrey R.;Steinle, Nanette I.;Grobbee, Diederick E.;Arking, Dan E.;Kardia, Sharon L.;Morrison, Alanna C.;Hernandez, Dena;Najjar, Samer;McArdle, Wendy L.;Hadley, David;Brown, Morris J.;Connell, John M.;Hingorani, Aroon D.;Day, Ian N. M.;Lawlor, Debbie A.;Beilby, John P.;Lawrence, Robert W.;Clarke, Robert;Hopewell, Jemma C.;Ongen, Halit;Dreisbach, Albert W.;Li, Yali;Young, J. Hunter;Bis, Joshua C.;Kahonen, Mika;Viikari, Jorma;Adair, Linda S.;Lee, Nanette R.;Chen, Ming-Huei;Olden, Matthias;Pattaro, Cristian;Bolton, Judith A. Hoffman;Koettgen, Anna;Bergmann, Sven;Mooser, Vincent;Chaturvedi, Nish;Frayling, Timothy M.;Islam, Muhammad;Jafar, Tazeen H.;Erdmann, Jeanette;Kulkarni, Smita R.;Bornstein, Stefan R.;Graessler, Juergen;Groop, Leif;Voight, Benjamin F.;Kettunen, Johannes;Howard, Philip;Taylor, Andrew;Guarrera, Simonetta;Ricceri, Fulvio;Emilsson, Valur;Plump, Andrew;Barroso, Ine S.;Khaw, Kay-Tee;Weder, Alan B.;Hunt, Steven C.;Sun, Yan V.;Bergman, Richard N.;Collins, Francis S.;Bonnycastle, Lori L.;Scott, Laura J.;Stringham, Heather M.;Peltonen, Leena;Perola, Markus;Vartiainen, Erkki;Brand, Stefan-Martin;Staessen, Jan A.;Wang, Thomas J.;Burton, Paul R.;Artigas, Maria Soler;Dong, Yanbin;Snieder, Harold;Wang, Xiaoling;Zhu, Haidong;Lohman, Kurt K.;Rudock, Megan E.;Heckbert, Susan R.;Smith, Nicholas L.;Wiggins, Kerri L.;Doumatey, Ayo;Shriner, Daniel;Veldre, Gudrun;Viigimaa, Margus;Kinra, Sanjay;Prabhakaran, Dorairaj;Tripathy, Vikal;Langefeld, Carl D.;Rosengren, Annika;Thelle, Dag S.;Corsi, Anna Maria;Singleton, Andrew;Forrester, Terrence;Hilton, Gina;McKenzie, Colin A.;Salako, Tunde;Iwai, Naoharu;Kita, Yoshikuni;Ogihara, Toshio;Ohkubo, Takayoshi;Okamura, Tomonori;Ueshima, Hirotsugu;Umemura, Satoshi;Eyheramendy, Susana;Meitinger, Thomas;Wichmann, H. -Erich;Cho, Yoon Shin;Kim, Hyung-Lae;Lee, Jong-Young;Scott, James;Sehmi, Joban S.;Zhang, Weihua;Hedblad, Bo;Nilsson, Peter;Smith, George Davey;Wong, Andrew;Narisu, Narisu;Stancakova, Alena;Raffel, Leslie J.;Yao, Jie;Kathiresan, Sekar;O'Donnell, Christopher J.;Schwartz, Stephen M.;Ikram, M. Arfan;Longstreth, W. T., Jr.;Mosley, Thomas H.;Seshadri, Sudha;Shrine, Nick R. G.;Wain, Louise V.;Morken, Mario A.;Swift, Amy J.;Laitinen, Jaana;Prokopenko, Inga;Zitting, Paavo;Cooper, Jackie A.;Humphries, Steve E.;Danesh, John;Rasheed, Asif;Goel, Anuj;Hamsten, Anders;Watkins, Hugh;Bakker, Stephan J. L.;van Gilst, Wiek H.;Janipalli, Charles S.;Mani, K. Radha;Yajnik, Chittaranjan S.;Hofman, Albert;Mattace-Raso, Francesco U. S.;Oostra, Ben A.;Demirkan, Ayse;Isaacs, Aaron;Rivadeneira, Fernando;Lakatta, Edward G.;Orru, Marco;Scuteri, Angelo;Ala-Korpela, Mika;Kangas, Antti J.;Lyytikainen, Leo-Pekka;Soininen, Pasi;Tukiainen, Taru;Wurtz, Peter;Ong, Rick Twee-Hee;Doerr, Marcus;Kroemer, Heyo K.;Voelker, Uwe;Voelzke, Henry;Galan, Pilar;Hercberg, Serge;Lathrop, Mark;Zelenika, Diana;Deloukas, Panos;Mangino, Massimo;Spector, Tim D.;Zhai, Guangju;Meschia, James F.;Nalls, Michael A.;Sharma, Pankaj;Terzic, Janos;Kumar, M. V. Kranthi;Denniff, Matthew;Zukowska-Szczechowska, Ewa;Wagenknecht, Lynne E.;Fowkes, F. Gerald R.;Charchar, Fadi J.;Schwarz, Peter E. H.;Hayward, Caroline;Guo, Xiuqing;Rotimi, Charles;Bots, Michiel L.;Brand, Eva;Samani, Nilesh J.;Polasek, Ozren;Talmud, Philippa J.;Nyberg, Fredrik;Kuh, Diana;Laan, Maris;Hveem, Kristian;Palmer, Lyle J.;van der Schouw, Yvonne T.;Casas, Juan P.;Mohlke, Karen L.;Vineis, Paolo;Raitakari, Olli;Ganesh, Santhi K.;Wong, Tien Y.;Tai, E. Shyong;Cooper, Richard S.;Laakso, Markku;Rao, Dabeeru C.;Harris, Tamara B.;Morris, Richard W.;Dominiczak, Anna F.;Kivimaki, Mika;Marmot, Michael G.;Miki, Tetsuro;Saleheen, Danish;Chandak, Giriraj R.;Coresh, Josef;Navis, Gerjan;Salomaa, Veikko;Han, Bok-Ghee;Zhu, Xiaofeng;Kooner, Jaspal S.;Melander, Olle;Ridker, Paul M.;Bandinelli, Stefania;Gyllensten, Ulf B.;Wright, Alan F.;Wilson, James F.;Ferrucci, Luigi;Farrall, Martin;Tuomilehto, Jaakko;Pramstaller, Peter P.;Elosua, Roberto;Soranzo, Nicole;Sijbrands, Eric J. G.;Altshuler, David;Loos, Ruth J. F.;Shuldiner, Alan R.;Gieger, Christian;Meneton, Pierre;Uitterlinden, Andre G.;Wareham, Nicholas J.;Gudnason, Vilmundur;Rotter, Jerome I.;Rettig, Rainer;Uda, Manuela;Strachan, David P.;Witteman, Jacqueline C. M.;Hartikainen, Anna-Liisa;Beckmann, Jacques S.;Boerwinkle, Eric;Vasan, Ramachandran S.;Boehnke, Michael;Larson, Martin G.;Jarvelin, Marjo-Riitta;Psaty, Bruce M.;Abecasis, Goncalo R.;Chakravarti, Aravinda;Elliott, Paul;van Duijn, Cornelia M.;Newton-Cheh, Christopher;Levy, Daniel;Caulfield, Mark J.;Johnson, Toby
通讯作者:
Johnson, Toby