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.
Department of Internal Medicine, Rotterdam, The Netherlands.
Fernando
F
Rivadeneira
Unnur
U
Styrkársdottir
Karol
K
Estrada
Bjarni V
BV
Halldórsson
Yi-Hsiang
YH
Hsu
J Brent
JB
Richards
M Carola
MC
Zillikens
Fotini K
FK
Kavvoura
Najaf
N
Amin
Yurii S
YS
Aulchenko
L Adrienne
LA
Cupples
Panagiotis
P
Deloukas
Serkalem
S
Demissie
Elin
E
Grundberg
Albert
A
Hofman
Augustine
A
Kong
David
D
Karasik
Joyce B
JB
van Meurs
Ben
B
Oostra
Tomi
T
Pastinen
Huibert A P
HA
Pols
Gunnar
G
Sigurdsson
Nicole
N
Soranzo
Gudmar
G
Thorleifsson
Unnur
U
Thorsteinsdottir
Frances M K
FM
Williams
Scott G
SG
Wilson
Yanhua
Y
Zhou
Stuart H
SH
Ralston
Cornelia M
CM
van Duijn
Timothy
T
Spector
Douglas P
DP
Kiel
Kari
K
Stefansson
John P A
JP
Ioannidis
André G
AG
Uitterlinden
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