Meta-analysis of genome-wide association studies confirms a susceptibility locus for knee osteoarthritis on chromosome 7q22.
OBJECTIVE
Osteoarthritis (OA) is the most prevalent form of arthritis and accounts for substantial morbidity and disability, particularly in older people. It is characterised by changes in joint structure, including degeneration of the articular cartilage, and its aetiology is multifactorial with a strong postulated genetic component.


METHODS
A meta-analysis was performed of four genome-wide association (GWA) studies of 2371 cases of knee OA and 35 909 controls in Caucasian populations. Replication of the top hits was attempted with data from 10 additional replication datasets.


RESULTS
With a cumulative sample size of 6709 cases and 44 439 controls, one genome-wide significant locus was identified on chromosome 7q22 for knee OA (rs4730250, p=9.2 × 10⁻⁹), thereby confirming its role as a susceptibility locus for OA.


CONCLUSIONS
The associated signal is located within a large (500 kb) linkage disequilibrium block that contains six genes: PRKAR2B (protein kinase, cAMP-dependent, regulatory, type II, β), HPB1 (HMG-box transcription factor 1), COG5 (component of oligomeric golgi complex 5), GPR22 (G protein-coupled receptor 22), DUS4L (dihydrouridine synthase 4-like) and BCAP29 (B cell receptor-associated protein 29). Gene expression analyses of the (six) genes in primary cells derived from different joint tissues confirmed expression of all the genes in the joint environment.
Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
Evangelos
E
Evangelou
Ana M
AM
Valdes
Hanneke J M
HJ
Kerkhof
Unnur
U
Styrkarsdottir
Yanyan
Y
Zhu
Ingrid
I
Meulenbelt
Rik J
RJ
Lories
Fotini B
FB
Karassa
Przemko
P
Tylzanowski
Steffan D
SD
Bos
Toru
T
Akune
Nigel K
NK
Arden
Andrew
A
Carr
Kay
K
Chapman
L Adrienne
LA
Cupples
Jin
J
Dai
Panos
P
Deloukas
Michael
M
Doherty
Sally
S
Doherty
Gunnar
G
Engstrom
Antonio
A
Gonzalez
Bjarni V
BV
Halldorsson
Christina L
CL
Hammond
Deborah J
DJ
Hart
Hafdis
H
Helgadottir
Albert
A
Hofman
Shiro
S
Ikegawa
Thorvaldur
T
Ingvarsson
Qing
Q
Jiang
Helgi
H
Jonsson
Jaakko
J
Kaprio
Hiroshi
H
Kawaguchi
Kalle
K
Kisand
Margreet
M
Kloppenburg
Urho M
UM
Kujala
L Stefan
LS
Lohmander
John
J
Loughlin
Frank P
FP
Luyten
Akihiko
A
Mabuchi
Andrew
A
McCaskie
Masahiro
M
Nakajima
Peter M
PM
Nilsson
Nao
N
Nishida
William E R
WE
Ollier
Kalliope
K
Panoutsopoulou
Tom
T
van de Putte
Stuart H
SH
Ralston
Fernado
F
Rivadeneira
Janna
J
Saarela
Stefan
S
Schulte-Merker
Dongquan
D
Shi
P Eline
PE
Slagboom
Akihiro
A
Sudo
Agu
A
Tamm
Ann
A
Tamm
Gudmar
G
Thorleifsson
Unnur
U
Thorsteinsdottir
Aspasia
A
Tsezou
Gillian A
GA
Wallis
J Mark
JM
Wilkinson
Noriko
N
Yoshimura
Eleftheria
E
Zeggini
Guangju
G
Zhai
Feng
F
Zhang
Ingileif
I
Jonsdottir
Andre G
AG
Uitterlinden
David T
DT
Felson
Joyce B
JB
van Meurs
Kari
K
Stefansson
John P A
JP
Ioannidis
Timothy D
TD
Spector
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult