Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies.
Bone mineral density (BMD) is a heritable complex trait used in the clinical diagnosis of osteoporosis and the assessment of fracture risk. We performed meta-analysis of five genome-wide association studies of femoral neck and lumbar spine BMD in 19,195 subjects of Northern European descent. We identified 20 BMD loci that reached genome-wide significance (GWS; P < 5 x 10(-8)), of which 13 map to regions not previously associated with this trait: 1p31.3 (GPR177), 2p21 (SPTBN1), 3p22 (CTNNB1), 4q21.1 (MEPE), 5q14 (MEF2C), 7p14 (STARD3NL), 7q21.3 (FLJ42280), 11p11.2 (LRP4, ARHGAP1, F2), 11p14.1 (DCDC5), 11p15 (SOX6), 16q24 (FOXL1), 17q21 (HDAC5) and 17q12 (CRHR1). The meta-analysis also confirmed at GWS level seven known BMD loci on 1p36 (ZBTB40), 6q25 (ESR1), 8q24 (TNFRSF11B), 11q13.4 (LRP5), 12q13 (SP7), 13q14 (TNFSF11) and 18q21 (TNFRSF11A). The many SNPs associated with BMD map to genes in signaling pathways with relevance to bone metabolism and highlight the complex genetic architecture that underlies osteoporosis and variation in BMD.
Rivadeneira
Fernando
F
Department of Internal Medicine, Rotterdam, The Netherlands.
Styrkársdottir
Unnur
U
Estrada
Karol
K
Halldórsson
Bjarni V
BV
Hsu
Yi-Hsiang
YH
Richards
J Brent
JB
Zillikens
M Carola
MC
Kavvoura
Fotini K
FK
Amin
Najaf
N
Aulchenko
Yurii S
YS
Cupples
L Adrienne
LA
Deloukas
Panagiotis
P
Demissie
Serkalem
S
Grundberg
Elin
E
Hofman
Albert
A
Kong
Augustine
A
Karasik
David
D
van Meurs
Joyce B
JB
Oostra
Ben
B
Pastinen
Tomi
T
Pols
Huibert A P
HA
Sigurdsson
Gunnar
G
Soranzo
Nicole
N
Thorleifsson
Gudmar
G
Thorsteinsdottir
Unnur
U
Williams
Frances M K
FM
Wilson
Scott G
SG
Zhou
Yanhua
Y
Ralston
Stuart H
SH
van Duijn
Cornelia M
CM
Spector
Timothy
T
Kiel
Douglas P
DP
Stefansson
Kari
K
Ioannidis
John P A
JP
Uitterlinden
André G
AG
D015519:Bone Density / Q000235:genetics*; D005269:Femur / Q000502:physiology; D050723:Fractures, Bone / Q000235:genetics; D005786:Gene Expression Regulation; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008159:Lumbar Vertebrae / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012307:Risk Factors; D044465:White People / Q000235:genetics