Cortical bone health shows significant linkage to chromosomes 2p, 3p, and 17q in 10-year-old children

Duren, Dana L.; Blangero, John; Sherwood, Richard J.; Šešelj, Maja; Dyer, Thomas D.; Cole, Shelley A.; Lee, Miryoung; Choh, Audrey C.; Chumlea, Wm. Cameron; Czerwinski, Stefan A.; Towne, Bradford

doi:10.1016/j.bone.2011.08.024

Cited by 10 publications

(10 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, having “the gene” for osteoporosis is not an inevitable sentence for weak or brittle bones, but rather causes a predisposition to such conditions. Our own work has successfully identified genomic regions influencing bone at specific childhood ages (Duren et al, 2011), with some regions containing attractive candidate genes such as the oxytocin receptor gene that has implications for bone gain and loss throughout life given the receptor’s binding affinity to estrogen. As mentioned above, environmental and functional factors play a large role in the resultant bone morphology.…”

mentioning

confidence: 99%

Skeletal growth and the changing genetic landscape during childhood and adulthood

Duren

Šešelj

Froehle

et al. 2012

American J Phys Anthropol

Self Cite

View full text Add to dashboard Cite

Growth, development, and decline of the human skeleton are of central importance to physical anthropology. All processes of skeletal growth (longitudinal growth as well as gains and losses of bone mass) are subject to environmental and genetic influences. These influences, and their relative contributions to the phenotype, can be asserted at any stage of life. We present here the gross phenotypic and genetic landscapes of four skeletal traits, and show how they vary across the life span. Phenotypic sex differences are found in bone diameter and cortical index (a ratio of cortical thickness over bone diameter) at a very early age and continue throughout most of life. Sexual dimorphism in summed cortical thickness and bone length, however, is not evident until shortly after the pubertal growth spurt. Genetic contributions (heritability) to these skeletal phenotypes are generally moderate to high. Bone length and bone diameter (which both scale with body size) tend to have the highest heritability, with heritability of bone length fairly stable across ages (with a notable dip in early childhood) and that of bone diameter peaking in early childhood. The bone traits summed cortical thickness and cortical index, that may better reflect bone mass, a more plastic phenomenon, have slightly lower genetic influences, on average. Results from our phenotypic and genetic landscapes serve three key purposes: demonstration of the integrated nature of the genetic and environmental underpinnings of skeletal form; identification of periods of bone’s relative sensitivity to genetic and environmental influences; and stimulation of hypotheses predicting the effects of exposure to environmental variables on the skeleton, given variation in the underlying genetic architecture.

show abstract

mentioning

confidence: 99%

Skeletal growth and the changing genetic landscape during childhood and adulthood

Duren

Šešelj

Froehle

et al. 2012

American J Phys Anthropol

Self Cite

View full text Add to dashboard Cite

show abstract

“…Most importantly, we lacked a suitable comparison for our study. To our knowledge, the only genome-wide publication on genetic contributions to bone phenotypes in 10-year-old children was that of Duren and colleagues [ 39 ]. They performed a search for loci linked to metacarpal thickness in 10-year-old children participating in the Fels Longitudinal Study.…”

Section: Discussionmentioning

confidence: 99%

Genetic factors influencing bone mineral content in a black South African population

May¹,

Pettifor²,

Norris³

et al. 2013

J Bone Miner Metab

View full text Add to dashboard Cite

Bone mass differs according to ethnic classification, with individuals of African ancestry attaining the highest measurements across numerous skeletal sites. Elevated bone mass is even maintained in those individuals exposed to adverse environmental factors, suggesting a prominent genetic effect that may have clinical or therapeutic value. Using a candidate gene approach, we investigated associations of six candidate genes (ESR1, TNFRSF11A, TNFRSF11B, TNFSF11, SOST and SPP1) with bone mass at the hip and lumbar spine amongst pre-pubertal black South African children (mean age 10.6 years) who formed part of the longitudinal Birth to Twenty cohort. 151 black children were genotyped at 366 polymorphic loci, including 112 previously associated and 254 tagging single nucleotide polymorphisms (SNPs). Linear regression was used to highlight significant associations whilst adjusting for height, weight, sex and bone area. Twenty-seven markers (8 previously associated and 19 tag SNPs; P < 0.05) were found to be associated with either femoral neck (18) or lumbar spine (9) bone mineral content. These signals were derived from three genes, namely ESR1 (17), TNFRSF11B (9) and SPP1 (1). One marker (rs2485209) maintained its association with the femoral neck after correction for multiple testing (P = 0.038). When compared to results amongst Caucasian adults, we detected differences with respect to associated skeletal sites. Allele frequencies and linkage disequilibrium patterns were also significantly different between populations. Hence, our results support the existence of a strong genetic effect acting at the femoral neck in black South African children, whilst simultaneously highlighting possible causes that account for inter-ethnic bone mass diversity.

show abstract

“…Bone diameter and medial and lateral cortical thicknesses were measured using the software measurement tool at the calculated midpoint of the diaphysis. A measure of bone accrual, the cortical index, was calculated as the ratio of medial + lateral cortical thickness to bone diameter [38]. A measure of skeletal maturity was calculated as the ratio of the distal epiphyseal width and the distal metaphyseal width [39].…”

Section: Methodsmentioning

confidence: 99%

Bone growth in juvenile rhesus monkeys is influenced by 5HTTLPR polymorphisms and interactions between 5HTTLPR polymorphisms and fluoxetine

Golub

Bulleri

Hogrefe

et al. 2015

Bone

Self Cite

View full text Add to dashboard Cite

Male rhesus monkeys received a therapeutic oral dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine daily from 1 to 3 years of age. Puberty is typically initiated between 2 and 3 years of age in male rhesus and reproductive maturity is reached at 4 years. The study group was genotyped for polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (SERT) genes that affect serotonin neurotransmission. Growth was assessed with morphometrics at 4 month intervals and radiographs of long bones were taken at 12 month intervals to evaluate skeletal growth and maturation. No effects of fluoxetine, or MAOA or SERT genotype were found for growth during the first year of the study. Linear growth began to slow during the second year of the study and serotonin reuptake transporter (SERT) long polymorphic region (5HTTLPR) polymorphism effects with drug interactions emerged. Monkeys with two SERT 5HTTLPR L alleles (LL, putative greater transcription) had 25–39% less long bone growth, depending on the bone, than monkeys with one S and one L allele (SL). More advanced skeletal maturity was also seen in the LL group, suggesting earlier onset of puberty. An interaction between 5HTTLPR polymorphisms and fluoxetine was identified for femur and tibia growth; the 5HTTLPR effect was seen in controls (40% less growth for LL) but not in the fluoxetine treated group (10% less growth for LL). A role for serotonin in peripubertal skeletal growth and maturation has not previously been investigated but may be relevant to treatment of children with SSRIs.

show abstract

Cortical bone health shows significant linkage to chromosomes 2p, 3p, and 17q in 10-year-old children

Cited by 10 publications

References 59 publications

Skeletal growth and the changing genetic landscape during childhood and adulthood

Skeletal growth and the changing genetic landscape during childhood and adulthood

Genetic factors influencing bone mineral content in a black South African population

Bone growth in juvenile rhesus monkeys is influenced by 5HTTLPR polymorphisms and interactions between 5HTTLPR polymorphisms and fluoxetine

Contact Info

Product

Resources

About