Genome-wide association study of bone mineral density in premenopausal European-American women and replication in African-American women.
BACKGROUND
Several genome-wide association studies (GWAS) have been performed to identify genes contributing to bone mineral density (BMD), typically in samples of elderly women and men.


OBJECTIVE
The objective of the study was to identify genes contributing to BMD in premenopausal women.


METHODS
GWAS using the Illumina 610Quad array in premenopausal European-American (EA) women and replication of the top 50 single-nucleotide polymorphisms (SNPs) for two BMD measures in African-American (AA) women.


METHODS
Subjects included 1524 premenopausal EA women aged 20-45 yr from 762 sibships and 669 AA premenopausal women aged 20-44 yr from 383 sibships.


METHODS
There were no interventions.


METHODS
BMD was measured at the lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Age- and weight-adjusted BMD values were tested for association with each SNP, with P values determined by permutation.


RESULTS
SNPs in CATSPERB on chromosome 14 provided evidence of association with femoral neck BMD (rs1298989, P = 2.7 x 10(-5); rs1285635, P = 3.0 x 10(-5)) in the EA women, and some supporting evidence was also observed with these SNPs in the AA women (rs1285635, P = 0.003). Genes identified in other BMD GWAS studies, including IBSP and ADAMTS18, were also among the most significant findings in our GWAS.


CONCLUSIONS
Evidence of association to several novel loci was detected in a GWAS of premenopausal EA women, and SNPs in one of these loci also provided supporting evidence in a sample of AA women.
Koller
Daniel L
DL
Departments of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. dkoller@iupui.edu
Ichikawa
Shoji
S
Lai
Dongbing
D
Padgett
Leah R
LR
Doheny
Kimberly F
KF
Pugh
Elizabeth
E
Paschall
Justin
J
Hui
Siu L
SL
Edenberg
Howard J
HJ
Xuei
Xiaoling
X
Peacock
Munro
M
Econs
Michael J
MJ
Foroud
Tatiana
T
D015502:Absorptiometry, Photon; D000328:Adult; D000483:Alleles; D044383:Black People; D015519:Bone Density / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D007196:Indiana / Q000453:epidemiology; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017697:Premenopause / Q000235:genetics* / Q000502:physiology*; D011786:Quality Control; D015203:Reproducibility of Results; D013131:Spine / Q000033:anatomy & histology; D044465:White People; D001741:Black or African American