title: Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women.
abstract: Osteoporosis is a complex disease with both genetic and environmental risk factors. A major determinant of osteoporotic fractures is peak BMD obtained during young adulthood. We previously reported linkage of chromosome 1q (LOD = 4.3) with variation in spinal areal BMD in healthy premenopausal white women. In this study, we used a two-stage genotyping approach to identify genes in the linked region that contributed to the variation of femoral neck and lumbar spine areal BMD. In the first stage, 654 SNPs across the linked region were genotyped in a sample of 1309 premenopausal white women. The most significant evidence of association for lumbar spine (p = 1.3 x 10(-6)) was found with rs1127091 in the GATAD2B gene. In the second stage, 52 SNPs around this candidate gene were genotyped in an expanded sample of 1692 white women. Significant evidence of association with spinal BMD (p < 10(-5)), and to a lesser extent with femoral neck BMD, was observed with eight SNPs within a single 230-kb linkage disequilibrium (LD) block. The most significant SNP (p = 3.4 x 10(-7)) accounted for >2.5% of the variation in spinal BMD in these women. The 230-kb LD block contains 11 genes, but because of the extensive LD, the specific gene(s) contributing to the variation in BMD could not be determined. In conclusion, the significant association between spinal BMD and SNPs in the 230-kb LD block in chromosome 1q indicates that genetic factor(s) in this block plays an important role in peak spinal BMD in healthy premenopausal white women.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202-5121, USA.
authors.forename: Shoji
authors.initials: S
authors.lastname: Ichikawa
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Koller
authors.forename: Leah R
authors.initials: LR
authors.lastname: Curry
authors.forename: Dongbing
authors.initials: D
authors.lastname: Lai
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Xuei
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Pugh
authors.forename: Ya-Yu
authors.initials: YY
authors.lastname: Tsai
authors.forename: Kimberly F
authors.initials: KF
authors.lastname: Doheny
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Edenberg
authors.forename: Siu L
authors.initials: SL
authors.lastname: Hui
authors.forename: Tatiana
authors.initials: T
authors.lastname: Foroud
authors.forename: Munro
authors.initials: M
authors.lastname: Peacock
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Econs
mesh_terms: D000328:Adult; D015519:Bone Density / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1; D005260:Female; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017697:Premenopause; D044465:White People