Dataset Information

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.

SUBMITTER: Ichikawa S

PROVIDER: S-EPMC2684159 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women.

Ichikawa Shoji S Koller Daniel L DL Curry Leah R LR Lai Dongbing D Xuei Xiaoling X Pugh Elizabeth W EW Tsai Ya-Yu YY Doheny Kimberly F KF Edenberg Howard J HJ Hui Siu L SL Foroud Tatiana T Peacock Munro M Econs Michael J MJ

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 20081001 10

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, ...[more]

PMID: 18505370

Similar Datasets

Project description:Linkage disequilibrium (LD) analysis provides information on the evolutionary aspects of populations. Recently, haplotype blocks have been used to increase the power of quantitative trait loci detection in genome-wide association studies and the prediction accuracy of genomic selection. Our objectives were as follows: to compare the degree of LD, LD decay, and LD decay extent in popcorn populations; to characterize the number and length of haplotype blocks in the populations; and to determine whether maize chromosomes also have a pattern of interspaced regions of high and low rates of recombination. We used a biparental population, a synthetic, and a breeding population, genotyped for approximately 75,000 single nucleotide polymorphisms (SNPs). The sample size ranged from 190 to 192 plants. For the whole-genome LD and haplotype block analyses, we assumed a window of 500 kb. To characterize the block and step patterns of LD in the populations, we constructed LD maps by chromosome, defining a cold spot as a chromosome segment including SNPs with the same LDU position. The LD and haplotype block analyses were also performed at the intragenic level, selecting 12 genes related to zein, starch, cellulose, and fatty acid biosynthesis. The populations with the higher and lower frequencies of |D'| values greater than 0.75 were the biparental (65-74%) and the breeding population (26-58%), respectively. There were slight differences between the populations regarding the average distance for SNPs with |D'| values greater than 0.75 (in the range of approximately 207 to 229 kb). The level of LD expressed by the r2 values was low in the populations (0.02, 0.04, and 0.04, on average) but comparable to some non-isolated human populations. The frequency of r2 values greater than 0.75 was lower in the biparental population (0.2-0.5%) and higher in the other populations (0.2-1.6%). The average distance for SNPs with r2 values greater than 0.75 was much higher in the biparental population (approximately 80 to 126 kb). In the other populations, the ranges were approximately 6 to 19 and 6 to 35 kb. The heatmaps for the regions covered by the first 100 SNPs in each chromosome, in each population (1 to 3.3 Mb, approximately), provided evidence that the comparatively few high r2 values (close to 1.0) occurred only for SNPs in close proximity, especially in the synthetic and breeding populations. Due to the reduced number of SNPs in the haplotype blocks (2 to 3) in the populations, it is not expected advantage of a haplotype-based association study as well as genomic selection along generations. The results concerning LD decay (rapid decay after 5-10 kb) and LD decay extent (along up to 300 kb) are in the range observed with maize inbred line panels. The LD maps indicate that maize chromosomes had a pattern of regions of extensive LD interspaced with regions of low LD. However, our simulated LD map provides evidence that this pattern can reflect regions with differences in allele frequencies and LD levels (expressed by |D'|) and not regions with high and low rates of recombination.

Project description:SummaryOsteoporosis is an increasing health problem in postmenopausal women. Our findings indicated that long-term brisk walking with a volume greater than 16 per week is effective for improving BMD in premenopausal women.PurposeTo examine the effects of brisk walking on bone mineral density (BMD) in premenopausal women, and further determine the effective frequency, intensity, time and volume (frequency x duration) of brisk walking for training strategy prescription.Methods222 healthy premenopausal women were recruited for BMD measurement. According to the survey of their physical activity level, 84 subjects (age: 46±1.8) whose physical activity index ≥40 were categorized into the brisk walking group, and 138 subjects (age: 47±2.2) whose physical activity index <40 were assigned to the sedentary group. The BMD of these two groups were statistically compared with an independent t test. Next, 35 subjects from the original sedentary group were recruited for BMD measurement after 2-year moderate brisk walking. According to the volume of physical activity per week, they were divided into the control group (n = 10, aged 49±0.9), volume 8 group (n = 4, aged 48±1.2), volume 12 group (n = 7, aged 49±1.4), volume 16 group (n = 8, aged 49±1.3), and volume 20 group (n = 6, aged 49±1.5). ANOVA was used to analyze BMD before and after brisk walking among the five groups.ResultsThe BMD in the brisk walking group (1.00±0.008 g/cm2) was significantly higher than that in the sedentary group (0.89±0.008 g/cm2) (P<0.001). Stepwise regression analysis revealed that the volume of brisk walking was significantly correlated with BMD (P<0.001). In particular, brisk walking with a volume greater than 16 (a score of duration up to 4 and a score of frequency up to 4 or 5) per week is effective for improving BMD in premenopausal women (P = 0.03, P = 0.002, respectively).ConclusionsLong-term brisk walking is an efficient way to improve BMD. Taking brisk walks for 30 minutes per day 3 or more times per week (volume>16) is recommended to prevent bone loss in premenopausal women.

Dataset Information

Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women.

Publications

Identification of a linkage disequilibrium block in chromosome 1q associated with BMD in premenopausal white women.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets