title: Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.
abstract: Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed approximately 19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated approximately 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Niall
authors.initials: N
authors.lastname: Cardin
authors.forename: Richard D
authors.initials: RD
authors.lastname: Pearson
authors.forename: Vincent
authors.initials: V
authors.lastname: Plagnol
authors.forename: Samuel
authors.initials: S
authors.lastname: Robson
authors.forename: Damjan
authors.initials: D
authors.lastname: Vukcevic
authors.forename: Chris
authors.initials: C
authors.lastname: Barnes
authors.forename: Donald F
authors.initials: DF
authors.lastname: Conrad
authors.forename: Eleni
authors.initials: E
authors.lastname: Giannoulatou
authors.forename: Chris
authors.initials: C
authors.lastname: Holmes
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Marchini
authors.forename: Kathy
authors.initials: K
authors.lastname: Stirrups
authors.forename: Martin D
authors.initials: MD
authors.lastname: Tobin
authors.forename: Louise V
authors.initials: LV
authors.lastname: Wain
authors.forename: Chris
authors.initials: C
authors.lastname: Yau
authors.forename: Jan
authors.initials: J
authors.lastname: Aerts
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmad
authors.forename: T Daniel
authors.initials: TD
authors.lastname: Andrews
authors.forename: Hazel
authors.initials: H
authors.lastname: Arbury
authors.forename: Anthony
authors.initials: A
authors.lastname: Attwood
authors.forename: Adam
authors.initials: A
authors.lastname: Auton
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Ball
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Balmforth
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Barrett
authors.forename: Inês
authors.initials: I
authors.lastname: Barroso
authors.forename: Anne
authors.initials: A
authors.lastname: Barton
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Bennett
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Bhaskar
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Blaszczyk
authors.forename: John
authors.initials: J
authors.lastname: Bowes
authors.forename: Oliver J
authors.initials: OJ
authors.lastname: Brand
authors.forename: Peter S
authors.initials: PS
authors.lastname: Braund
authors.forename: Francesca
authors.initials: F
authors.lastname: Bredin
authors.forename: Gerome
authors.initials: G
authors.lastname: Breen
authors.forename: Morris J
authors.initials: MJ
authors.lastname: Brown
authors.forename: Ian N
authors.initials: IN
authors.lastname: Bruce
authors.forename: Jaswinder
authors.initials: J
authors.lastname: Bull
authors.forename: Oliver S
authors.initials: OS
authors.lastname: Burren
authors.forename: John
authors.initials: J
authors.lastname: Burton
authors.forename: Jake
authors.initials: J
authors.lastname: Byrnes
authors.forename: Sian
authors.initials: S
authors.lastname: Caesar
authors.forename: Chris M
authors.initials: CM
authors.lastname: Clee
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Coffey
authors.forename: John M C
authors.initials: JM
authors.lastname: Connell
authors.forename: Jason D
authors.initials: JD
authors.lastname: Cooper
authors.forename: Anna F
authors.initials: AF
authors.lastname: Dominiczak
authors.forename: Kate
authors.initials: K
authors.lastname: Downes
authors.forename: Hazel E
authors.initials: HE
authors.lastname: Drummond
authors.forename: Darshna
authors.initials: D
authors.lastname: Dudakia
authors.forename: Andrew
authors.initials: A
authors.lastname: Dunham
authors.forename: Bernadette
authors.initials: B
authors.lastname: Ebbs
authors.forename: Diana
authors.initials: D
authors.lastname: Eccles
authors.forename: Sarah
authors.initials: S
authors.lastname: Edkins
authors.forename: Cathryn
authors.initials: C
authors.lastname: Edwards
authors.forename: Anna
authors.initials: A
authors.lastname: Elliot
authors.forename: Paul
authors.initials: P
authors.lastname: Emery
authors.forename: David M
authors.initials: DM
authors.lastname: Evans
authors.forename: Gareth
authors.initials: G
authors.lastname: Evans
authors.forename: Steve
authors.initials: S
authors.lastname: Eyre
authors.forename: Anne
authors.initials: A
authors.lastname: Farmer
authors.forename: I Nicol
authors.initials: IN
authors.lastname: Ferrier
authors.forename: Lars
authors.initials: L
authors.lastname: Feuk
authors.forename: Tomas
authors.initials: T
authors.lastname: Fitzgerald
authors.forename: Edward
authors.initials: E
authors.lastname: Flynn
authors.forename: Alistair
authors.initials: A
authors.lastname: Forbes
authors.forename: Liz
authors.initials: L
authors.lastname: Forty
authors.forename: Jayne A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Freathy
authors.forename: Polly
authors.initials: P
authors.lastname: Gibbs
authors.forename: Paul
authors.initials: P
authors.lastname: Gilbert
authors.forename: Omer
authors.initials: O
authors.lastname: Gokumen
authors.forename: Katherine
authors.initials: K
authors.lastname: Gordon-Smith
authors.forename: Emma
authors.initials: E
authors.lastname: Gray
authors.forename: Elaine
authors.initials: E
authors.lastname: Green
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Groves
authors.forename: Detelina
authors.initials: D
authors.lastname: Grozeva
authors.forename: Rhian
authors.initials: R
authors.lastname: Gwilliam
authors.forename: Anita
authors.initials: A
authors.lastname: Hall
authors.forename: Naomi
authors.initials: N
authors.lastname: Hammond
authors.forename: Matt
authors.initials: M
authors.lastname: Hardy
authors.forename: Pile
authors.initials: P
authors.lastname: Harrison
authors.forename: Neelam
authors.initials: N
authors.lastname: Hassanali
authors.forename: Husam
authors.initials: H
authors.lastname: Hebaishi
authors.forename: Sarah
authors.initials: S
authors.lastname: Hines
authors.forename: Anne
authors.initials: A
authors.lastname: Hinks
authors.forename: Graham A
authors.initials: GA
authors.lastname: Hitman
authors.forename: Lynne
authors.initials: L
authors.lastname: Hocking
authors.forename: Eleanor
authors.initials: E
authors.lastname: Howard
authors.forename: Philip
authors.initials: P
authors.lastname: Howard
authors.forename: Joanna M M
authors.initials: JM
authors.lastname: Howson
authors.forename: Debbie
authors.initials: D
authors.lastname: Hughes
authors.forename: Sarah
authors.initials: S
authors.lastname: Hunt
authors.forename: John D
authors.initials: JD
authors.lastname: Isaacs
authors.forename: Mahim
authors.initials: M
authors.lastname: Jain
authors.forename: Derek P
authors.initials: DP
authors.lastname: Jewell
authors.forename: Toby
authors.initials: T
authors.lastname: Johnson
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Jolley
authors.forename: Ian R
authors.initials: IR
authors.lastname: Jones
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Jones
authors.forename: George
authors.initials: G
authors.lastname: Kirov
authors.forename: Cordelia F
authors.initials: CF
authors.lastname: Langford
authors.forename: Hana
authors.initials: H
authors.lastname: Lango-Allen
authors.forename: G Mark
authors.initials: GM
authors.lastname: Lathrop
authors.forename: James
authors.initials: J
authors.lastname: Lee
authors.forename: Kate L
authors.initials: KL
authors.lastname: Lee
authors.forename: Charlie
authors.initials: C
authors.lastname: Lees
authors.forename: Kevin
authors.initials: K
authors.lastname: Lewis
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Meeta
authors.initials: M
authors.lastname: Maisuria-Armer
authors.forename: Julian
authors.initials: J
authors.lastname: Maller
authors.forename: John
authors.initials: J
authors.lastname: Mansfield
authors.forename: Paul
authors.initials: P
authors.lastname: Martin
authors.forename: Dunecan C O
authors.initials: DC
authors.lastname: Massey
authors.forename: Wendy L
authors.initials: WL
authors.lastname: McArdle
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Kirsten E
authors.initials: KE
authors.lastname: McLay
authors.forename: Alex
authors.initials: A
authors.lastname: Mentzer
authors.forename: Michael L
authors.initials: ML
authors.lastname: Mimmack
authors.forename: Ann E
authors.initials: AE
authors.lastname: Morgan
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
authors.forename: Craig
authors.initials: C
authors.lastname: Mowat
authors.forename: Simon
authors.initials: S
authors.lastname: Myers
authors.forename: William
authors.initials: W
authors.lastname: Newman
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Nimmo
authors.forename: Michael C
authors.initials: MC
authors.lastname: O'Donovan
authors.forename: Abiodun
authors.initials: A
authors.lastname: Onipinla
authors.forename: Ifejinelo
authors.initials: I
authors.lastname: Onyiah
authors.forename: Nigel R
authors.initials: NR
authors.lastname: Ovington
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Owen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Palin
authors.forename: Kirstie
authors.initials: K
authors.lastname: Parnell
authors.forename: David
authors.initials: D
authors.lastname: Pernet
authors.forename: John R B
authors.initials: JR
authors.lastname: Perry
authors.forename: Anne
authors.initials: A
authors.lastname: Phillips
authors.forename: Dalila
authors.initials: D
authors.lastname: Pinto
authors.forename: Natalie J
authors.initials: NJ
authors.lastname: Prescott
authors.forename: Inga
authors.initials: I
authors.lastname: Prokopenko
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.forename: Suzanne
authors.initials: S
authors.lastname: Rafelt
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Rayner
authors.forename: Richard
authors.initials: R
authors.lastname: Redon
authors.forename: David M
authors.initials: DM
authors.lastname: Reid
authors.lastname: Renwick
authors.forename: Susan M
authors.initials: SM
authors.lastname: Ring
authors.forename: Neil
authors.initials: N
authors.lastname: Robertson
authors.forename: Ellie
authors.initials: E
authors.lastname: Russell
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: Jennifer G
authors.initials: JG
authors.lastname: Sambrook
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Sanderson
authors.forename: Helen
authors.initials: H
authors.lastname: Schuilenburg
authors.forename: Carol E
authors.initials: CE
authors.lastname: Scott
authors.forename: Richard
authors.initials: R
authors.lastname: Scott
authors.forename: Sheila
authors.initials: S
authors.lastname: Seal
authors.forename: Sue
authors.initials: S
authors.lastname: Shaw-Hawkins
authors.forename: Beverley M
authors.initials: BM
authors.lastname: Shields
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Simmonds
authors.forename: Debbie J
authors.initials: DJ
authors.lastname: Smyth
authors.forename: Elilan
authors.initials: E
authors.lastname: Somaskantharajah
authors.forename: Katarina
authors.initials: K
authors.lastname: Spanova
authors.forename: Sophia
authors.initials: S
authors.lastname: Steer
authors.forename: Jonathan
authors.initials: J
authors.lastname: Stephens
authors.forename: Helen E
authors.initials: HE
authors.lastname: Stevens
authors.forename: Millicent A
authors.initials: MA
authors.lastname: Stone
authors.forename: Zhan
authors.initials: Z
authors.lastname: Su
authors.forename: Deborah P M
authors.initials: DP
authors.lastname: Symmons
authors.forename: John R
authors.initials: JR
authors.lastname: Thompson
authors.forename: Wendy
authors.initials: W
authors.lastname: Thomson
authors.forename: Mary E
authors.initials: ME
authors.lastname: Travers
authors.forename: Clare
authors.initials: C
authors.lastname: Turnbull
authors.forename: Armand
authors.initials: A
authors.lastname: Valsesia
authors.forename: Mark
authors.initials: M
authors.lastname: Walker
authors.forename: Neil M
authors.initials: NM
authors.lastname: Walker
authors.forename: Chris
authors.initials: C
authors.lastname: Wallace
authors.forename: Margaret
authors.initials: M
authors.lastname: Warren-Perry
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Watkins
authors.forename: John
authors.initials: J
authors.lastname: Webster
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Wilson
authors.forename: Matthew
authors.initials: M
authors.lastname: Woodburn
authors.forename: B Paul
authors.initials: BP
authors.lastname: Wordsworth
authors.forename: Allan H
authors.initials: AH
authors.lastname: Young
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
authors.forename: Nigel P
authors.initials: NP
authors.lastname: Carter
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Charles
authors.initials: C
authors.lastname: Lee
authors.forename: Gil
authors.initials: G
authors.lastname: McVean
authors.forename: Patricia B
authors.initials: PB
authors.lastname: Munroe
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Sawcer
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.forename: David P
authors.initials: DP
authors.lastname: Strachan
authors.forename: Chris
authors.initials: C
authors.lastname: Tyler-Smith
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Brown
authors.forename: Paul R
authors.initials: PR
authors.lastname: Burton
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Caulfield
authors.forename: Alastair
authors.initials: A
authors.lastname: Compston
authors.forename: Martin
authors.initials: M
authors.lastname: Farrall
authors.forename: Stephen C L
authors.initials: SC
authors.lastname: Gough
authors.forename: Alistair S
authors.initials: AS
authors.lastname: Hall
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Adrian V S
authors.initials: AV
authors.lastname: Hill
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Mathew
authors.forename: Marcus
authors.initials: M
authors.lastname: Pembrey
authors.forename: Jack
authors.initials: J
authors.lastname: Satsangi
authors.forename: Michael R
authors.initials: MR
authors.lastname: Stratton
authors.forename: Jane
authors.initials: J
authors.lastname: Worthington
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: Audrey
authors.initials: A
authors.lastname: Duncanson
authors.forename: Dominic P
authors.initials: DP
authors.lastname: Kwiatkowski
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Willem
authors.initials: W
authors.lastname: Ouwehand
authors.forename: Miles
authors.initials: M
authors.lastname: Parkes
authors.forename: Nazneen
authors.initials: N
authors.lastname: Rahman
authors.forename: John A
authors.initials: JA
authors.lastname: Todd
authors.forename: Nilesh J
authors.initials: NJ
authors.lastname: Samani
authors.forename: Peter
authors.initials: P
authors.lastname: Donnelly
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics; D016022:Case-Control Studies; D003424:Crohn Disease / Q000235:genetics; D056915:DNA Copy Number Variations / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics; D004194:Disease; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011786:Quality Control