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Genome-wide association studies of childhood bone health

Johnson, Kelly (2016) Genome-wide association studies of childhood bone health. Master's Thesis, University of Pittsburgh. (Unpublished)

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Osteoporosis is a major public health concern characterized by low bone mineral density (BMD) and deterioration of bone tissue, causing increased bone fragility and risk of fracture. Though current research has focused primarily on bone health in the elderly, early bone health, including peak BMD attainment, is a strong predictor of bone health later in life. Twin and family studies have demonstrated a strong genetic component in peak BMD, though the specific genes influencing variation in bone development are largely unknown. Moreover, the question of whether the genes influencing bone health during childhood are the same as those influencing bone health later in life is currently unknown. Therefore, to identify variants and genes implicated in childhood bone health, we performed separate genome-wide association studies (GWAS) for ten bone health phenotypes (bone mineral content [BMC] and BMD of the hip, spine, and head, BMC of the whole body, and four measures of hip geometry) in 296 Caucasian children aged 5 years (mean = 5.3) who were enrolled in the Iowa Bone Development Study. Linear regression while adjusting for sex, height, and weight was used to test 548,051 genetic polymorphisms and 7.4 million imputed variants for evidence of association. Genomic regions showing statistical association were scrutinized for relevant gene functions related to bone biology. Five genome- wide significant (P≤5x10-8) and 30 suggestive (P<10-6) loci were identified in total. Implicated genes may represent significant roles in the converging pathways that regulate BMD, embryonic bone development, and bone remodeling. Furthermore, understanding the genetic determinants of
bone health during childhood may have implications across the lifespan. Though osteoporosis is usually viewed as an age-related disorder, risk of osteoporosis is impacted much earlier in life, including phases of bone mineral acquisition during youth. Therefore, the public health significance of this study is that identifying the genetic factors contributing to early skeletal health may ultimately lead to screening programs, which identify children with a genetic predisposition to bone disease. This allows for targeted interventions to optimize bone health in adolescence, promote management of bone health across the lifespan, and lower risk for osteoporosis later in life.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Johnson, Kellykellyjohnson892@gmail.comKAJ68
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairShaffer, John Rjrs51@pitt.eduJRS51
Committee MemberKuipers, Allison Lindsaykuipers@pitt.eduKUIPERS
Committee MemberDurst, Andreaadurst@pitt.eduADURST
Date: 29 June 2016
Date Type: Publication
Defense Date: 5 April 2016
Approval Date: 29 June 2016
Submission Date: 28 April 2016
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 136
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Genetic Counseling
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: GWAS, bone, genetics, childhood
Date Deposited: 29 Jun 2016 18:04
Last Modified: 01 May 2018 05:15


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