A Pilot Genome-Wide Association Study in Postmenopausal Mexican-Mestizo Women Implicates the RMND1/CCDC170 Locus Is Associated with Bone Mineral Density

Abstract

To identify genetic variants influencing bone mineral density (BMD) in the Mexican-Mestizo population, we performed a GWAS for femoral neck (FN) and lumbar spine (LS) in Mexican-Mestizo postmenopausal women. In the discovery sample, 300,000 SNPs were genotyped in a cohort of 411 postmenopausal women and seven SNPs were analyzed in the replication cohort (n = 420). The combined results of a meta-analysis from the discovery and replication samples identified two loci, RMND1 (rs6904364, P = 2.77 × 10−4) and CCDC170 (rs17081341, P = 1.62 × 10−5), associated with FN BMD. We also compared our results with those of the Genetic Factors for Osteoporosis (GEFOS) Consortium meta-analysis. The comparison revealed two loci previously reported in the GEFOS meta-analysis: SOX6 (rs7128738) and PKDCC (rs11887431) associated with FN and LS BMD, respectively, in our study population. Interestingly, rs17081341 rare in Caucasians (minor allele frequency < 0.03) was found in high frequency in our population, which suggests that this association could be specific to non-Caucasian populations. In conclusion, the first pilot Mexican GWA study of BMD confirmed previously identified loci and also demonstrated the importance of studying variability in diverse populations and/or specific populations.

The Variant rs1784042 of the SIDT2 Gene is Associated with Metabolic Syndrome through Low HDL-c Levels in a Mexican Population

“…The pilot GWAS with TC, Low-Density Lipoprotein cholesterol (LDL-c), HDL-c, glucose and TG serum levels was carried out using the EPACS Genome Analysis tool as follows: we performed a quantitative linear Wald Test model using residual inverse normal transformation of age, body mass index (BMI) and two ancestry principal components (ancestry correction). The study design and methodology are described in detail elsewhere [ 29 , 30 ]. Briefly, the median age of the cohort was 61 years (55–68), median BMI was 27.5 (25.3–34.3) and 68.2% had MetS.…”

“…The present study is part of a large-scale genetic study to identify genetic variants affecting bone mineral density (BMD) and related quantitative metabolic traits in the Mexican population [ 29 , 30 ].…”

“…Previously, we carried out a pilot GWAS in Mexican-Mestizo postmenopausal women ( n = 411), which represent a subsample of the Health Workers Cohort Study (HWCS) over 61 years of age. In that study, we identified SNPs significantly associated with several metabolic traits [ 29 , 30 ]. The relative low frequency of some functional variants of SIDT2 in several populations, provides a unique opportunity to assess association with clinical/metabolic traits, in admixed populations, such as the Mexican-Mestizo.…”

Functional characterization of the C7ORF76 genomic region, a prominent GWAS signal for osteoporosis in 7q21.3

“…found a LS-BMD associated signal within LOC100506136 in a Mexican-Mestizo cohort [60]. These studies suggest that this lncRNA could be involved in osteoporosis pathogenesis.…”

SOX6 rs7117858 polymorphism is associated with osteoporosis and obesity‐related phenotypes

“…Recent GWAS and candidate gene studies have found a relationship between different genetic variants in SOX6 regions and osteoporosis phenotypes (femoral neck, lumbar spine and wrist BMD) [22][23][24][25][26][27][28][29][30][31] . Interestingly, the rs7117858 SNP located downstream of the SOX6 gene have been reported to be associated with BMD in Caucasian and Chinese populations [23][24][25][26]32 .…”