Human genetic variation and its contribution to complex traits

被引：723

作者：

Frazer, Kelly A. ^{[1
]}

Murray, Sarah S.

Schork, Nicholas J.

Topol, Eric J.

机构：

[1] Scripps Translat Sci Inst, La Jolla, CA 92037 USA

来源：

NATURE REVIEWS GENETICS | 2009年 / 10卷 / 04期

基金：

美国国家卫生研究院;

关键词：

GENOME-WIDE ASSOCIATION; COPY-NUMBER VARIATION; PROSTATE-CANCER RISK; STRUCTURAL VARIATION; SUSCEPTIBILITY LOCI; COMMON VARIANT; RARE VARIANTS; LINKAGE DISEQUILIBRIUM; POPULATION-GENETICS; SKIN PIGMENTATION;

D O I：

10.1038/nrg2554

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The last few years have seen extensive efforts to catalogue human genetic variation and correlate it with phenotypic differences. Most common SNPs have now been assessed in genome-wide studies for statistical associations with many complex traits, including many important common diseases. Although these studies have provided new biological insights, only a limited amount of the heritable component of any complex trait has been identified and it remains a challenge to elucidate the functional link between associated variants and phenotypic traits. Technological advances, such as the ability to detect rare and structural variants, and a clear understanding of the challenges in linking different types of variation with phenotype, will be essential for future progress.

引用

页码：241 / 251

页数：11

共 132 条

[91] Variants in MTNR1B influence fasting glucose levels [J].

Prokopenko, Inga ;

Langenberg, Claudia ;

Florez, Jose C. ;

Saxena, Richa ;

Soranzo, Nicole ;

Thorleifsson, Gudmar ;

Loos, Ruth J. F. ;

Manning, Alisa K. ;

Jackson, Anne U. ;

Aulchenko, Yurii ;

Potter, Simon C. ;

Erdos, Michael R. ;

Sanna, Serena ;

Hottenga, Jouke-Jan ;

Wheeler, Eleanor ;

Kaakinen, Marika ;

Lyssenko, Valeriya ;

Chen, Wei-Min ;

Ahmadi, Kourosh ;

Beckmann, Jacques S. ;

Bergman, Richard N. ;

Bochud, Murielle ;

Bonnycastle, Lori L. ;

Buchanan, Thomas A. ;

Cao, Antonio ;

Cervino, Alessandra ;

Coin, Lachlan ;

Collins, Francis S. ;

Crisponi, Laura ;

De Geus, Eco J. C. ;

Dehghan, Abbas ;

Deloukas, Panos ;

Doney, Alex S. F. ;

Elliott, Paul ;

Freimer, Nelson ;

Gateva, Vesela ;

Herder, Christian ;

Hofman, Albert ;

Hughes, Thomas E. ;

Hunt, Sarah ;

Illig, Thomas ;

Inouye, Michael ;

Isomaa, Bo ;

Johnson, Toby ;

Kong, Augustine ;

Krestyaninova, Maria ;

Kuusisto, Johanna ;

Laakso, Markku ;

Lim, Noha ;

Lindblad, Ulf .

NATURE GENETICS, 2009, 41 (01) :77-81

[92] Global variation in copy number in the human genome [J].

Redon, Richard ;

Ishikawa, Shumpei ;

Fitch, Karen R. ;

Feuk, Lars ;

Perry, George H. ;

Andrews, T. Daniel ;

Fiegler, Heike ;

Shapero, Michael H. ;

Carson, Andrew R. ;

Chen, Wenwei ;

Cho, Eun Kyung ;

Dallaire, Stephanie ;

Freeman, Jennifer L. ;

Gonzalez, Juan R. ;

Gratacos, Monica ;

Huang, Jing ;

Kalaitzopoulos, Dimitrios ;

Komura, Daisuke ;

MacDonald, Jeffrey R. ;

Marshall, Christian R. ;

Mei, Rui ;

Montgomery, Lyndal ;

Nishimura, Kunihiro ;

Okamura, Kohji ;

Shen, Fan ;

Somerville, Martin J. ;

Tchinda, Joelle ;

Valsesia, Armand ;

Woodwark, Cara ;

Yang, Fengtang ;

Zhang, Junjun ;

Zerjal, Tatiana ;

Zhang, Jane ;

Armengol, Lluis ;

Conrad, Donald F. ;

Estivill, Xavier ;

Tyler-Smith, Chris ;

Carter, Nigel P. ;

Aburatani, Hiroyuki ;

Lee, Charles ;

Jones, Keith W. ;

Scherer, Stephen W. ;

Hurles, Matthew E. .

NATURE, 2006, 444 (7118) :444-454

[93] On the allelic spectrum of human disease [J].

Reich, DE ;

Lander, ES .

TRENDS IN GENETICS, 2001, 17 (09) :502-510

[94] Male-pattern baldness susceptibility locus at 20p11 [J].

Richards, J. Brent ;

Yuan, Xin ;

Geller, Frank ;

Waterworth, Dawn ;

Bataille, Veronique ;

Glass, Daniel ;

Song, Kijoung ;

Waeber, Gerard ;

Vollenweider, Peter ;

Aben, Katja K. H. ;

Kiemeney, Lambertus A. ;

Walters, Bragi ;

Soranzo, Nicole ;

Thorsteinsdottir, Unnur ;

Kong, Augustine ;

Rafnar, Thorunn ;

Deloukas, Panos ;

Sulem, Patrick ;

Stefansson, Hreinn ;

Stefansson, Kari ;

Spector, Tim D. ;

Mooser, Vincent .

NATURE GENETICS, 2008, 40 (11) :1282-1284

[95] Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis [J].

Rioux, John D. ;

Xavier, Ramnik J. ;

Taylor, Kent D. ;

Silverberg, Mark S. ;

Goyette, Philippe ;

Huett, Alan ;

Green, Todd ;

Kuballa, Petric ;

Barmada, M. Michael ;

Datta, Lisa Wu ;

Shugart, Yin Yao ;

Griffiths, Anne M. ;

Targan, Stephan R. ;

Ippoliti, Andrew F. ;

Bernard, Edmond-Jean ;

Mei, Ling ;

Nicolae, Dan L. ;

Regueiro, Miguel ;

Schumm, L. Philip ;

Steinhart, A. Hillary ;

Rotter, Jerome I. ;

Duerr, Richard H. ;

Cho, Judy H. ;

Daly, Mark J. ;

Brant, Steven R. .

NATURE GENETICS, 2007, 39 (05) :596-604

[96] Population-based resequencing of ANGPTL4 uncovers variations that reduce triglycerides and increase HDL [J].

Romeo, Stefano ;

Pennacchio, Len A. ;

Fu, Yunxin ;

Boerwinkle, Eric ;

Tybjaerg-Hansen, Anne ;

Hobbs, Helen H. ;

Cohen, Jonathan C. .

NATURE GENETICS, 2007, 39 (04) :513-516

[97] Genome-wide association analysis of metabolic traits in a birth cohort from a founder population [J].

Sabatti, Chiara ;

Service, Susan K. ;

Hartikainen, Anna-Liisa ;

Pouta, Anneli ;

Ripatti, Samuli ;

Brodsky, Jae ;

Jones, Chris G. ;

Zaitlen, Noah A. ;

Varilo, Teppo ;

Kaakinen, Marika ;

Sovio, Ulla ;

Ruokonen, Aimo ;

Laitinen, Jaana ;

Jakkula, Eveliina ;

Coin, Lachlan ;

Hoggart, Clive ;

Collins, Andrew ;

Turunen, Hannu ;

Gabriel, Stacey ;

Elliot, Paul ;

McCarthy, Mark I. ;

Daly, Mark J. ;

Jarvelin, Marjo-Riitta ;

Freimer, Nelson B. ;

Peltonen, Leena .

NATURE GENETICS, 2009, 41 (01) :35-46

[98] Genomewide association analysis of coronary artery disease [J].

Samani, Nilesh J. ;

Erdmann, Jeanette ;

Hall, Alistair S. ;

Hengstenberg, Christian ;

Mangino, Massimo ;

Mayer, Bjoern ;

Dixon, Richard J. ;

Meitinger, Thomas ;

Braund, Peter ;

Wichmann, H.-Erich ;

Barrett, Jennifer H. ;

Koenig, Inke R. ;

Stevens, Suzanne E. ;

Szymczak, Silke ;

Tregouet, David-Alexandre ;

Iles, Mark M. ;

Pahlke, Friedrich ;

Pollard, Helen ;

Lieb, Wolfgang ;

Cambien, Francois ;

Fischer, Marcus ;

Ouwehand, Willem ;

Blankenberg, Stefan ;

Balmforth, Anthony J. ;

Baessler, Andrea ;

Ball, Stephen G. ;

Strom, Tim M. ;

Braenne, Ingrid ;

Gieger, Christian ;

Deloukas, Panos ;

Tobin, Martin D. ;

Ziegler, Andreas ;

Thompson, John R. ;

Schunkert, Heribert .

NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (05) :443-453

[99] Common variants in the GDF5-UQCC region are associated with variation in human height [J].

Sanna, Serena ;

Jackson, Anne U. ;

Nagaraja, Ramaiah ;

Willer, Cristen J. ;

Chen, Wei-Min ;

Bonnycastle, Lori L. ;

Shen, Haiqing ;

Timpson, Nicholas ;

Lettre, Guillaume ;

Usala, Gianluca ;

Chines, Peter S. ;

Stringham, Heather M. ;

Scott, Laura J. ;

Dei, Mariano ;

Lai, Sandra ;

Albai, Giuseppe ;

Crisponi, Laura ;

Naitza, Silvia ;

Doheny, Kimberly F. ;

Pugh, Elizabeth W. ;

Ben-Shlomo, Yoav ;

Ebrahim, Shah ;

Lawlor, Debbie A. ;

Bergman, Richard N. ;

Watanabe, Richard M. ;

Uda, Manuela ;

Tuomilehto, Jaakko ;

Coresh, Josef ;

Hirschhorn, Joel N. ;

Shuldiner, Alan R. ;

Schlessinger, David ;

Collins, Francis S. ;

Smith, George Davey ;

Boerwinkle, Eric ;

Cao, Antonio ;

Boehnke, Michael ;

Abecasis, Goncalo R. ;

Mohlke, Karen L. .

NATURE GENETICS, 2008, 40 (02) :198-203

[100] Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels [J].

Saxena, Richa ;

Voight, Benjamin F. ;

Lyssenko, Valeriya ;

Burtt, Noel P. ;

de Bakker, Paul I. W. ;

Chen, Hong ;

Roix, Jeffrey J. ;

Kathiresan, Sekar ;

Hirschhorn, Joel N. ;

Daly, Mark J. ;

Hughes, Thomas E. ;

Groop, Leif ;

Altshuler, David ;

Almgren, Peter ;

Florez, Jose C. ;

Meyer, Joanne ;

Ardlie, Kristin ;

Bostroem, Kristina Bengtsson ;

Isomaa, Bo ;

Lettre, Guillaume ;

Lindblad, Ulf ;

Lyon, Helen N. ;

Melander, Olle ;

Newton-Cheh, Christopher ;

Nilsson, Peter ;

Orho-Melander, Marju ;

Rastam, Lennart ;

Speliotes, Elizabeth K. ;

Taskinen, Marja-Riitta ;

Tuomi, Tiinamaija ;

Guiducci, Candace ;

Berglund, Anna ;

Carlson, Joyce ;

Gianniny, Lauren ;

Hackett, Rachel ;

Hall, Liselotte ;

Holmkvist, Johan ;

Laurila, Esa ;

Sjoegren, Marketa ;

Sterner, Maria ;

Surti, Aarti ;

Svensson, Margareta ;

Svensson, Malin ;

Tewhey, Ryan ;

Blumenstiel, Brendan ;

Parkin, Melissa ;

DeFelice, Matthew ;

Barry, Rachel ;

Brodeur, Wendy ;

Camarata, Jody .

SCIENCE, 2007, 316 (5829) :1331-1336

← 5 6 7 8 9 10 11 12 13 14 →