Genome-wide approaches for identifying genetic risk factors for osteoporosis

Abstract

Osteoporosis, the most common type of bone disease worldwide, is clinically characterized by low bone mineral density (BMD) and increased susceptibility to fracture. Multiple genetic and environmental factors and gene-environment interactions have been implicated in its pathogenesis. Osteoporosis has strong genetic determination, with the heritability of BMD estimated to be as high as 60%. More than 80 genes or genetic variants have been implicated in risk of osteoporosis by hypothesis-free genome-wide studies. However, these genes or genetic variants can only explain a small portion of BMD variation, suggesting that many other genes or genetic variants underlying osteoporosis risk await discovery. Here, we review recent progress in genome-wide studies of osteoporosis and discuss their implications for medicine and the major challenges in the field.

WNT3A gene polymorphisms are associated with bone mineral density variation in postmenopausal mestizo women of an urban Mexican population: findings of a pathway-based high-density single nucleotide screening

“…Potential reasons for this lack of association include differences in study methods and phenotype data, different genotyping methods and SNP genotype quality control, racial/ethnic differences in BMD, and insufficient sample size (Delezé et al 2000;Nam et al 2013;Wu et al 2013). Among other limitations, this study was based on a cross-sectional design, and the SNPs were selected from previous reports mainly in European populations.…”

“…Although genome-wide linkage and candidate gene association studies have revealed multiple genetic loci related to BMD variation, conflicting results have been observed and associations with several loci have not been replicated in other populations (Wu et al 2013). Several Wnt pathway genes have been associated with BMD phenotypes, ranging from osteoporosis (Butler et al 2011) to the high bone mass (HBM) (Boyden et al 2002).…”

“…The majority of studies examining the relationship of genetic factors with BMD variation and OP have been performed in populations of European and Asian ancestry Wu et al 2013). In the Mexican population, specific genetic factors of BMD variation remain largely unknown as only a few candidate gene studies have been reported in reduced samples and/or analyzing few SNPs (Lisker et al 2003;Gómez et al 2007;Magaña et al 2008;Falcón-Ramírez et al 2011;Rojano-Mejía et al 2013;Falcón-Ramírez et al 2013).…”

Multifactorial Pathogenesis of Osteoporosis and the Role of Genes of Canonical WNT-Signaling Pathway

“…С одной стороны, использование метода GWAS и изучение однонуклеотидных полиморфизмов (SNPs) позволило де-тализировать этиологически значимые изменения в генах, роль в развитии ОП которых была установлена во второй половине 1990-х и начале 2000-х годов. С другой стороны, при помощи полногеномного поиска ассоциаций были от-крыты новые гены-кандидаты [11,20,31].…”

A study of factors leading to osteo-penia in the community: BMD camp based approach

“…4 As it is established that bone density decreases with age, more people become osteoporotic with increasing age. 3 Bone mineral density is diagnosed using Dualenergy X-ray absorptiometry (DXA) in which bone mineral density level is less than or equal to 2.5 standard deviations below that of a young (30-40 year old 5,6 ), healthy adult women reference population. This is translated as a T-score.…”