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Disentangling the effects of body size and genetics on insulin-like growth factor-1 and its relationship to mortality

Sherlala, Rehab (2021) Disentangling the effects of body size and genetics on insulin-like growth factor-1 and its relationship to mortality. Doctoral Dissertation, University of Pittsburgh. (Unpublished)

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The number of Americans age 65 and older is expected to increase to over 98 million by 2060 and results in an increased demand for health services due to increased rates of aging-related diseases. Studies of traits that are associated with longevity, such as the insulin-like growth factor‑1 (IGF‑1) levels, may provide insights to mitigate effects of these diseases. The relationship between IGF‑1 and body mass index (BMI), another trait associated with morbidity and mortality, is unclear. Furthermore, only seven genetic loci are known to be associated with IGF‑1 levels. In this study, I analyzed data from the Long Life Family Study participants, a unique cohort of two-generation families. My analyses indicated that the relationship between IGF‑1 and BMI differs across age groups, and this pattern was also seen in non-Hispanic White, non-Hispanic Black, and Mexican American participants in the third National Health and Nutritional Examination Survey. Genetic analysis revealed a novel locus associated with IGF‑1 levels on chromosome 11 (LOD = 3.48) as well as a previously known region on chromosome 7p12.3 (p ≤ 0.00023), although the identity of the specific gene (or genes) involved is unclear. Greater serum IGF‑1 levels were associated with lower risk of mortality (HR = 0.61, 95% CI = 0.53–0.70, p = 1.4× 10−10), an association that was attenuated after adjusting for age; however, the genetic variants associated with IGF‑1 levels themselves were not associated with the risk of mortality. Additional genetic studies are required to elucidate the role that IGF‑1 plays in age-related morbidity and mortality. My study has contributed to our understanding of the interplay between genetic and environmental factors that influence IGF‑1 levels and this knowledge may enable the development of methods to mitigate the development of age-related diseases and improve public health.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Sherlala, Rehabras148@pitt.eduras1480000-0003-3528-9337
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee ChairMinster, Ryan
Committee MemberKammerer, Candace
Committee MemberFeingold,
Committee MemberAllison L. Kuipers, Allison
Date: 27 August 2021
Date Type: Publication
Defense Date: 8 April 2021
Approval Date: 27 August 2021
Submission Date: 9 August 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 134
Institution: University of Pittsburgh
Schools and Programs: School of Public Health > Public Health Genetics
Degree: PhD - Doctor of Philosophy
Thesis Type: Doctoral Dissertation
Refereed: Yes
Uncontrolled Keywords: dissertation
Date Deposited: 27 Aug 2021 17:40
Last Modified: 27 Aug 2023 05:15


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