School of Medicine and Health Sciences Poster Presentations

Title

An Intronic Variant in DCHS2 is Associated with Bone Mineral Density in Children and Young Adults

Document Type

Poster

Keywords

DCHS2; Bone Mineral Density; Osteoporosis; Bone Health

Publication Date

Spring 2017

Abstract

Purpose of Study: Fragility fractures lead to significant morbidity and mortality in seniors. Recently, Compressive Strength Index (CSI) has been validated as a predictor of hip fracture risk. Han et al. have identified 3 genes that may play a role in determining CSI in Caucasians and Asians: FADS1, FADS2 and DCHS2 containing SNPs (FADS1/rs174549; rs174583, FADS2/rs174577, DCHS2/rs7672337). This study sought to examine whether these polymorphisms also influence other measures of bone quality in children and young adults.

Methods: Cohorts: The Assessing Inherited Markers of Metabolic Syndrome in the Young (AIMMY) cohort included Caucasian males: N=55 (avg 24 yrs) and females: N=54 (avg 22 yrs). Total body and lumbar bone mineral density (BMD) were analyzed. The Bone Health Cohort included African American children (age 5-9): 46 males and 41 females. Phenotypes were total body minus head BMD and lumbar BMD. Genotyping: Three SNPs were genotyped using the Illumina Multi-Ethnic Genotyping Array. Rs7672337 was genotyped utilizing a Taqman assay. Subjects and SNPs that fell below the quality thresholds were eliminated from the data set. The relationship between genotype and phenotype was tested using ANCOVA models where phenotype was the independent variable, genotype was the dependent variable, and age was a co-variant. For those ANCOVA models using the additive genetic model, where a statistically significant overall F-test was observed, post-hoc pair-wise comparisons between genotypes were performed. Post-hoc p-values were adjusted for multiple comparisons using the Sidak method.

Results: In the AIMMY cohort, lumbar BMD was found to be significantly associated with rs7672337 (DCHS2) in Caucasian females (p=0.047). No other significant associations were seen within the AIMMY or Bone Health cohorts.

Conclusion: An association was seen when observing the variant rs7672337 near the DCHS2 gene and lumbar BMD in female young adults from the AIMMY cohort. With all other conducted analysis, no significant association was uncovered. This suggests DCHS2, FADS1 and FADS2 do not play a role in total BMD or lumbar BMD development. Furthermore, this could suggest that other factors within the two measures, CSI and ALM, play a more prominent role than opposed to BMD. While the BMD measurement used was primarily hip BMD, if association with hip BMD was strong, then an association with total BMD should have been observed. As this was not the case, this could suggest that DCHS2, FADS1 and FADS2 have a stronger association with femoral neck area and/or weight.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

Open Access

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Comments

Poster to be presented at GW Annual Research Days 2017.

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An Intronic Variant in DCHS2 is Associated with Bone Mineral Density in Children and Young Adults

Purpose of Study: Fragility fractures lead to significant morbidity and mortality in seniors. Recently, Compressive Strength Index (CSI) has been validated as a predictor of hip fracture risk. Han et al. have identified 3 genes that may play a role in determining CSI in Caucasians and Asians: FADS1, FADS2 and DCHS2 containing SNPs (FADS1/rs174549; rs174583, FADS2/rs174577, DCHS2/rs7672337). This study sought to examine whether these polymorphisms also influence other measures of bone quality in children and young adults.

Methods: Cohorts: The Assessing Inherited Markers of Metabolic Syndrome in the Young (AIMMY) cohort included Caucasian males: N=55 (avg 24 yrs) and females: N=54 (avg 22 yrs). Total body and lumbar bone mineral density (BMD) were analyzed. The Bone Health Cohort included African American children (age 5-9): 46 males and 41 females. Phenotypes were total body minus head BMD and lumbar BMD. Genotyping: Three SNPs were genotyped using the Illumina Multi-Ethnic Genotyping Array. Rs7672337 was genotyped utilizing a Taqman assay. Subjects and SNPs that fell below the quality thresholds were eliminated from the data set. The relationship between genotype and phenotype was tested using ANCOVA models where phenotype was the independent variable, genotype was the dependent variable, and age was a co-variant. For those ANCOVA models using the additive genetic model, where a statistically significant overall F-test was observed, post-hoc pair-wise comparisons between genotypes were performed. Post-hoc p-values were adjusted for multiple comparisons using the Sidak method.

Results: In the AIMMY cohort, lumbar BMD was found to be significantly associated with rs7672337 (DCHS2) in Caucasian females (p=0.047). No other significant associations were seen within the AIMMY or Bone Health cohorts.

Conclusion: An association was seen when observing the variant rs7672337 near the DCHS2 gene and lumbar BMD in female young adults from the AIMMY cohort. With all other conducted analysis, no significant association was uncovered. This suggests DCHS2, FADS1 and FADS2 do not play a role in total BMD or lumbar BMD development. Furthermore, this could suggest that other factors within the two measures, CSI and ALM, play a more prominent role than opposed to BMD. While the BMD measurement used was primarily hip BMD, if association with hip BMD was strong, then an association with total BMD should have been observed. As this was not the case, this could suggest that DCHS2, FADS1 and FADS2 have a stronger association with femoral neck area and/or weight.