Quantitative Trait Locus on Chromosome 1q Influences Bone Loss in Young Mexican American Adults

Abstract

Bone loss occurs as early as the third decade and its cumulative effect throughout adulthood may impact risk for osteoporosis in later life, however, the genes and environmental factors influencing early bone loss are largely unknown. We investigated the role of genes in the change in bone mineral density (BMD) in participants in the San Antonio Family Osteoporosis Study. BMD change in 327 Mexican Americans (ages 25-45 years) from 32 extended pedigrees was calculated from DXA measurements at baseline and follow-up (3.5 to 8.9 years later). Family-based likelihood methods were used to estimate heritability (h(2)) and perform autosome-wide linkage analysis for BMD change of the proximal femur and forearm and to estimate heritability for BMD change of lumbar spine. BMD change was significantly heritable for total hip, ultradistal radius, and 33% radius (h(2) = 0.34, 0.34, and 0.27, respectively; p < 0.03 for all), modestly heritable for femoral neck (h(2) = 0.22; p = 0.06) and not heritable for spine BMD. Covariates associated with BMD change included age, sex, baseline BMD, menopause, body mass index, and interim BMI change, and accounted for 6% to 24% of phenotype variation. A significant quantitative trait locus (LOD = 3.6) for femoral neck BMD change was observed on chromosome 1q23. In conclusion, we observed that change in BMD in young adults is heritable and performed one of the first linkage studies for BMD change. Linkage to chromosome 1q23 suggests that this region may harbor one or more genes involved in regulating early BMD change of the femoral neck.