TY - JOUR
T1 - A Method to Exploit the Structure of Genetic Ancestry Space to Enhance Case-Control Studies
AU - The International IBD Genetics Consortium
AU - Bodea, Corneliu A.
AU - Neale, Benjamin M.
AU - Ripke, Stephan
AU - Barclay, Murray
AU - Peyrin-Biroulet, Laurent
AU - Chamaillard, Mathias
AU - Colombel, Jean Frederick
AU - Cottone, Mario
AU - Croft, Anthony
AU - D'Incà, Renata
AU - Halfvarson, Jonas
AU - Hanigan, Katherine
AU - Henderson, Paul
AU - Hugot, Jean Pierre
AU - Karban, Amir
AU - Kennedy, Nicholas A.
AU - Khan, Mohammed Azam
AU - Lémann, Marc
AU - Levine, Arie
AU - Massey, Dunecan
AU - Milla, Monica
AU - Montgomery, Grant W.
AU - Ng, Sok Meng Evelyn
AU - Oikonomou, Ioannis
AU - Peeters, Harald
AU - Proctor, Deborah D.
AU - Rahier, Jean Francois
AU - Roberts, Rebecca L.
AU - Rutgeerts, Paul
AU - Seibold, Frank
AU - Stronati, Laura
AU - Taylor, Kirstin M.
AU - Törkvist, Leif
AU - Ublick, Kullak
AU - Van Limbergen, Johan
AU - Van Gossum, Andre
AU - Vatn, Morten H.
AU - Zhang, Hu
AU - Zhang, Wei
AU - Andrews, Jane M.
AU - Bampton, Peter A.
AU - Florin, Timothy H.
AU - Gearry, Richard
AU - Krishnaprasad, Krupa
AU - Lawrance, Ian C.
AU - Mahy, Gillian
AU - Radford-Smith, Graham
AU - Roberts, Rebecca L.
AU - Simms, Lisa A.
AU - Amininijad, Leila
AU - Cleynen, Isabelle
AU - Dewit, Olivier
AU - Franchimont, Denis
AU - Georges, Michel
AU - Laukens, Debby
AU - Theatre, Emilie
AU - Vermeire, Severine
AU - Aumais, Guy
AU - Baidoo, Leonard
AU - Barrie III, Arthur M.
AU - Beck, Karen
AU - Bernard, Edmond Jean
AU - Binion, David G.
AU - Bitton, Alain
AU - Brant, Steve R.
AU - Cho, Judy H.
AU - Cohen, Albert
AU - Croitoru, Kenneth
AU - Datta, Lisa W.
AU - Deslandres, Colette
AU - Duerr, Richard H.
AU - Dutridge, Debra
AU - Ferguson, John
AU - Fultz, Joann
AU - Goyette, Philippe
AU - Greenberg, Gordon R.
AU - Haritunians, Talin
AU - Jobin, Gilles
AU - Katz, Seymour
AU - Lahaie, Raymond G.
AU - McGovern, Dermot P.
AU - Nelson, Linda
AU - Ng, Sok Meng
AU - Ning, Kaida
AU - Paré, Pierre
AU - Regueiro, Miguel D.
AU - Rioux, John D.
AU - Ruggiero, Elizabeth
AU - Schumm, L. Philip
AU - Schwartz, Marc
AU - Scott, Regan
AU - Sharma, Yashoda
AU - Silverberg, Mark S.
AU - Spears, Denise
AU - Steinhart, A. Hillary
AU - Stempak, Joanne M.
AU - Swoger, Jason M.
AU - Tsagarelis, Constantina
AU - Zhang, Clarence
AU - Zhao, Hongyu
AU - Aerts, Jan
AU - Ahmad, Tariq
AU - Arbury, Hazel
AU - Attwood, Anthony
AU - Auton, Adam
AU - Ball, Stephen G.
AU - Balmforth, Anthony J.
AU - Barnes, Chris
AU - Barrett, Jeffrey C.
AU - Barroso, Inês
AU - Barton, Anne
AU - Bennett, Amanda J.
AU - Bhaskar, Sanjeev
AU - Blaszczyk, Katarzyna
AU - Bowes, John
AU - Brand, Oliver J.
AU - Braund, Peter S.
AU - Bredin, Francesca
AU - Breen, Gerome
AU - Brown, Morris J.
AU - Bruce, Ian N.
AU - Bull, Jaswinder
AU - Burren, Oliver S.
AU - Burton, John
AU - Byrnes, Jake
AU - Caesar, Sian
AU - Cardin, Niall
AU - Clee, Chris M.
AU - Coffey, Alison J.
AU - Connell, John M.C.
AU - Conrad, Donald F.
AU - Cooper, Jason D.
AU - Dominiczak, Anna F.
AU - Downes, Kate
AU - Drummond, Hazel E.
AU - Dudakia, Darshna
AU - Dunham, Andrew
AU - Ebbs, Bernadette
AU - Eccles, Diana
AU - Edkins, Sarah
AU - Edwards, Cathryn
AU - Elliot, Anna
AU - Emery, Paul
AU - Evans, David M.
AU - Evans, Gareth
AU - Eyre, Steve
AU - Farmer, Anne
AU - Ferrier, Nicol
AU - Flynn, Edward
AU - Forbes, Alistair
AU - Forty, Liz
AU - Franklyn, Jayne A.
AU - Frayling, Timothy M.
AU - Freathy, Rachel M.
AU - Giannoulatou, Eleni
AU - Gibbs, Polly
AU - Gilbert, Paul
AU - Gordon-Smith, Katherine
AU - Gray, Emma
AU - Green, Elaine
AU - Groves, Chris J.
AU - Grozeva, Detelina
AU - Gwilliam, Rhian
AU - Hall, Anita
AU - Hammond, Naomi
AU - Hardy, Matt
AU - Harrison, Pile
AU - Hassanali, Neelam
AU - Hebaishi, Husam
AU - Hines, Sarah
AU - Hinks, Anne
AU - Hitman, Graham A.
AU - Hocking, Lynne
AU - Holmes, Chris
AU - Howard, Eleanor
AU - Howard, Philip
AU - Howson, Joanna M.M.
AU - Hughes, Debbie
AU - Hunt, Sarah
AU - Isaacs, John D.
AU - Jain, Mahim
AU - Jewell, Derek P.
AU - Johnson, Toby
AU - Jolley, Jennifer D.
AU - Jones, Ian R.
AU - Jones, Lisa A.
AU - Kirov, George
AU - Langford, Cordelia F.
AU - Lango-Allen, Hana
AU - Lathrop, G. Mark
AU - Lee, James
AU - Lee, Kate L.
AU - Lees, Charlie
AU - Lewis, Kevin
AU - Lindgren, Cecilia M.
AU - Maisuria-Armer, Meeta
AU - Maller, Julian
AU - Mansfield, John
AU - Marchini, Jonathan L.
AU - Martin, Paul
AU - Massey, Dunecan C.O.
AU - McArdle, Wendy L.
AU - McGuffin, Peter
AU - McLay, Kirsten E.
AU - McVean, Gil
AU - Mentzer, Alex
AU - Mimmack, Michael L.
AU - Morgan, Ann E.
AU - Morris, Andrew P.
AU - Mowat, Craig
AU - Munroe, Patricia B.
AU - Myers, Simon
AU - Newman, William
AU - Nimmo, Elaine R.
AU - O'Donovan, Michael C.
AU - Onipinla, Abiodun
AU - Ovington, Nigel R.
AU - Owen, Michael J.
AU - Palin, Kimmo
AU - Palotie, Aarno
AU - Parnell, Kirstie
AU - Pearson, Richard
AU - Pernet, David
AU - Perry, John R.B.
AU - Phillips, Anne
AU - Plagnol, Vincent
AU - Prescott, Natalie J.
AU - Prokopenko, Inga
AU - Quail, Michael A.
AU - Rafelt, Suzanne
AU - Rayner, Nigel W.
AU - Reid, David M.
AU - Renwick, Anthony
AU - Ring, Susan M.
AU - Robertson, Neil
AU - Robson, Samuel
AU - Russell, Ellie
AU - St Clair, David
AU - Sambrook, Jennifer G.
AU - Sanderson, Jeremy D.
AU - Sawcer, Stephen J.
AU - Schuilenburg, Helen
AU - Scott, Carol E.
AU - Scott, Richard
AU - Seal, Sheila
AU - Shaw-Hawkins, Sue
AU - Shields, Beverley M.
AU - Simmonds, Matthew J.
AU - Smyth, Debbie J.
AU - Somaskantharajah, Elilan
PY - 2016/5/5
Y1 - 2016/5/5
N2 - One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data.
AB - One goal of human genetics is to understand the genetic basis of disease, a challenge for diseases of complex inheritance because risk alleles are few relative to the vast set of benign variants. Risk variants are often sought by association studies in which allele frequencies in case subjects are contrasted with those from population-based samples used as control subjects. In an ideal world we would know population-level allele frequencies, releasing researchers to focus on case subjects. We argue this ideal is possible, at least theoretically, and we outline a path to achieving it in reality. If such a resource were to exist, it would yield ample savings and would facilitate the effective use of data repositories by removing administrative and technical barriers. We call this concept the Universal Control Repository Network (UNICORN), a means to perform association analyses without necessitating direct access to individual-level control data. Our approach to UNICORN uses existing genetic resources and various statistical tools to analyze these data, including hierarchical clustering with spectral analysis of ancestry; and empirical Bayesian analysis along with Gaussian spatial processes to estimate ancestry-specific allele frequencies. We demonstrate our approach using tens of thousands of control subjects from studies of Crohn disease, showing how it controls false positives, provides power similar to that achieved when all control data are directly accessible, and enhances power when control data are limiting or even imperfectly matched ancestrally. These results highlight how UNICORN can enable reliable, powerful, and convenient genetic association analyses without access to the individual-level data.
UR - http://www.scopus.com/inward/record.url?scp=84963574963&partnerID=8YFLogxK
U2 - 10.1016/j.ajhg.2016.02.025
DO - 10.1016/j.ajhg.2016.02.025
M3 - Article
C2 - 27087321
AN - SCOPUS:84963574963
SN - 0002-9297
VL - 98
SP - 857
EP - 868
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 5
ER -