Finding the missing heritability of complex diseases
Teri A. Manolio,Francis S. Collins,Nancy J. Cox,David Goldstein,Lucia A. Hindorff,David J. Hunter,Mark I. McCarthy,Erin M. Ramos,Lon R. Cardon,Aravinda Chakravarti,Judy H. Cho,Alan E. Guttmacher,Augustine Kong,Leonid Kruglyak,Leonid Kruglyak,Elaine R. Mardis,Charles N. Rotimi,Montgomery Slatkin,David Valle,Alice S. Whittemore,Michael Boehnke,Andrew G. Clark,Evan E. Eichler,Greg Gibson,Jonathan L. Haines,Trudy F. C. Mackay,Steven A. McCarroll,Peter M. Visscher +27 more
TL;DR: This paper examined potential sources of missing heritability and proposed research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
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Abstract: Genome-wide association studies have identified hundreds of genetic variants associated with complex human diseases and traits, and have provided valuable insights into their genetic architecture. Most variants identified so far confer relatively small increments in risk, and explain only a small proportion of familial clustering, leading many to question how the remaining, 'missing' heritability can be explained. Here we examine potential sources of missing heritability and propose research strategies, including and extending beyond current genome-wide association approaches, to illuminate the genetics of complex diseases and enhance its potential to enable effective disease prevention or treatment.
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Citations
Low-Frequency and Rare-Coding Variation Contributes to Multiple Sclerosis Risk
Mitja Mitrovic,Nikolaos A. Patsopoulos,Ashley Beecham,Theresa Dankowski,An Goris,Bénédicte Dubois,Marie B. D'hooghe,Robin Lemmens,Philip Van Damme,Helle Bach Søndergaard,Finn Sellebjerg,Per Soelberg Sørensen,Henrik Ullum,Lise Wegner Thoerner,Thomas Werge,Janna Saarela,Isabelle Cournu-Rebeix,Vincent Damotte,Bertrand Fontaine,Lena Guillot-Noel,Mark Lathrop,Sandra Vukusik,Pierre-Antoine Gourraud,Till F. M. Andlauer,Viola Pongratz,Dorothea Buck,Christiane Gasperi,Antonios Bayas,Christoph Heesen,Tania Kümpfel,Ralf A. Linker,Friedemann Paul,Martin Stangel,Björn Tackenberg,Florian Then Bergh,Clemens Warnke,Heinz Wiendl,Brigitte Wildemann,Uwe K. Zettl,Ulf Ziemann,Hayrettin Tumani,Ralf Gold,Verena Grummel,Bernhard Hemmer,Benjamin Knier,Christina M. Lill,Felix Luessi,Efthimios Dardiotis,Cristina Agliardi,Nadia Barizzone,Elisabetta Mascia,Luisa Bernardinelli,Giancarlo Comi,Daniele Cusi,Federica Esposito,Laura Ferrè,Cristoforo Comi,Daniela Galimberti,Maurizio Leone,Melissa Sorosina,Julia Y Mescheriakova,Rogier Q. Hintzen,Cornelia M. van Duijn,Charlotte E. Teunissen,Steffan D. Bos,Kjell-Morten Myhr,Elisabeth Gulowsen Celius,Benedicte A. Lie,Anne Spurkland,Manuel Comabella,Xavier Montalban,Lars Alfredsson,Pernilla Stridh,Jan Hillert,Maja Jagodic,Fredrik Piehl,Ilijas Jelcic,Roland Martin,Mireia Sospedra,Maria Ban,Clive Hawkins,Pirro G. Hysi,Seema Kalra,Fredrik Karpe,Jyoti Khadake,Genevieve Lachance,Matt J. Neville,Adam Santaniello,Stacy J. Caillier,Peter A. Calabresi,Bruce A.C. Cree,Anne H. Cross,Mary F. Davis,Jonathan L. Haines,Paul I.W. de Bakker,Silvia Delgado,Marieme Dembele,Keith R. Edwards,Kathryn C. Fitzgerald,Hakon Hakonarson,Ioanna Konidari,Ellen Lathi,Clara P. Manrique,Margaret A. Pericak-Vance,Laura Piccio,Cathy Schaefer,Cristin McCabe,Howard L. Weiner,Jacqueline I. Goldstein,Tomas Olsson,Georgios M. Hadjigeorgiou,Bruce V. Taylor,Lotti Tajouri,Jac Charlesworth,David R. Booth,Hanne F. Harbo,Adrian J. Ivinson,Stephen L. Hauser,Alastair Compston,Graeme Stewart,Frauke Zipp,Lisa F. Barcellos,Sergio E. Baranzini,Filippo Martinelli-Boneschi,Sandra D'Alfonso,Andreas Ziegler,Annette Bang Oturai,Jacob L. McCauley,Stephen Sawcer,Jorge R. Oksenberg,Philip L. De Jager,Ingrid Kockum,David A. Hafler,Chris Cotsapas +133 more
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Review article: the emerging role of genetics in precision medicine for patients with non-alcoholic steatohepatitis
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Lucia A. Hindorff,Praveen Sethupathy,Heather Junkins,Erin M. Ramos,Jayashri P. Mehta,Francis S. Collins,Teri A. Manolio +6 more
TL;DR: An online catalog of SNP-trait associations from published genome-wide association studies for use in investigating genomic characteristics of trait/disease-associated SNPs (TASs) is developed, well-suited to guide future investigations of the role of common variants in complex disease etiology.
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