Genome-Wide Association Analysis of Longitudinal Bone Mineral Content Data From the Iowa Bone Development Study

Camden P Bay; Steven M Levy; Kathleen F Janz; Brian J Smith; John R Shaffer; Mary L Marazita; Trudy L Burns

doi:10.1016/j.jocd.2019.09.005

Genome-Wide Association Analysis of Longitudinal Bone Mineral Content Data From the Iowa Bone Development Study

J Clin Densitom. 2021 Jan-Mar;24(1):44-54. doi: 10.1016/j.jocd.2019.09.005. Epub 2019 Sep 27.

Authors

Camden P Bay¹, Steven M Levy², Kathleen F Janz³, Brian J Smith⁴, John R Shaffer⁵, Mary L Marazita⁶, Trudy L Burns⁷

Affiliations

¹ Center for Clinical Investigation, Brigham & Women's Hospital, Boston, MA, USA. Electronic address: cpbay@bwh.harvard.edu.
² Department of Preventive and Community Dentistry, University of Iowa College of Dentistry, Iowa City, IA, USA; Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA.
³ Department of Health and Human Physiology, College of Liberal Arts and Sciences, University of Iowa, Iowa City, IA, USA.
⁴ Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, Iowa City, IA, USA; Department of Biostatistics, University of Iowa College of Public Health, Iowa City, IA, USA.
⁵ Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁶ Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USA; Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Clinical and Translational Science, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
⁷ Department of Epidemiology, University of Iowa College of Public Health, Iowa City, IA, USA.

Abstract

The foundation for osteoporosis risk is, in part, established during childhood, adolescence, and young adulthood, all periods of development when bone mass is acquired rapidly. The relative quantity of bone mass accrued is influenced by both lifestyle and genetic factors, although the genetic component is not yet well understood. The purpose of this study was to use a genome-wide association (GWA) analysis to discover single nucleotide polymorphisms (SNPs) associated with: (1) the sex-specific hip bone mineral content at approximately the age of 19 when the amount of bone accrued is near its peak; and (2) the sex-specific rate of hip bone mineral content accrual during the adolescent growth spurt. The Iowa Bone Development Study, a longitudinal cohort study exploring bone health in children, adolescents, and young adults was the source of data. From this cohort, n = 364 (190 females, 174 males) participants were included in GWA analyses to address (1) and n = 258 participants (125 females and 133 males) were included in GWA analyses to address (2). Twenty SNPS were detected having p < 1.0 × 10^-5. Of most biologic relevance were 2 suggestive SNPs (rs2051756 and rs2866908) detected in an intron of the DKK2 gene through the GWA analysis that explored peak bone mass in females.

Keywords: Adolescent bone development; DKK2; bone mass; genome-wide association study; longitudinal.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Bone Density* / genetics
Bone Development / genetics
Bone and Bones
Child
Female
Genome-Wide Association Study*
Humans
Longitudinal Studies
Male
Young Adult

Abstract

Publication types

MeSH terms

Grants and funding