Doctoral Candidate Rehab Sherlala of the Departmet of Human Genetics will defend her dissertation entitled "DISENTANGLING THE EFFECTS OF BODY SIZE AND GENETICS ON INSULIN-LIKE GROWTH FACTOR-1 AND ITS RELATIONSHIP TO MORTALITY."

ADVISOR: Ryan L. Minster, PhD, MSIS - Human Genetics

COMITTEE MEMBERS:

• Candace M. Kammerer, PhD - Human Genetics

• Allison L. Kuipers, PhD - Epidemiology

• Eleanor Feingold, PhD- Human Genetics

ABSTRACT:

The number of Americans age 65 and older is expected to increase to over 98 million by 2060 and resulting 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), 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 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 whites, blacks, and Hispanics who participated in the third National Health and Nutritional Examination Survey. Genetic analysis revealed a novel locus associated with IGF-1levels on chromosome 11 (LOD=3.48) as well as a previously known region on chromosome 7p12.3 (P ≤ 0.00023, although the identify of specific gene (or genes) involved is unclear.  Also, serum IGF-1 levels were associated with lower risk of mortality in the unadjusted analysis (HR=0.6, %95 CI=0.53-0.7), but genetic variants associated with IGF-1 levels were not associated with the risk of mortality (P > 0.05).  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.