Bad Genes or Genes Behaving Badly
Condition: Body Composition; Energy Balance; Metabolism
Study type: Observational

Summary: 
      A key factor in the determination of body composition over the lifecourse is fat accumulation
      during childhood. Periods of life associated with the greatest changes in organ development
      and growth, i.e. early childhood, have the most significant effect on body composition,
      energy balance, and metabolism. Early childhood (age 3 to 7 years) represents a critical
      transition for the basis of adaptability in body composition, due to the rapid growth and
      development that occurs. Plausibly the phenotype underlying obesity and related health risk
      may be determined by body composition during this critical period.

      Our previous research in children has consistently indicated that HA children accumulate
      greater amounts of fat, particularly in the intra-abdominal compartment, even at similar a
      BMI, and lower bone mineral content relative to EA children. The reason for these differences
      in body composition over the lifecourse is not clear.

      Racial/ethnic differences in risk factors for health, including 'thriftiness' in body fat
      accumulation are often evident before the age of 7, suggesting that the racial/ethnic
      differences in energy utilization and subsequent fat storage may be accounted for by genetic
      make-up, the environment (e.g. diet), or an interaction of the two. The physiologic or
      behavioral process(es) that cause(s) certain children to take a trajectory towards obesity
      while others accrue less fat is not known. However, the economic decision of fuel utilization
      is a physiologic trait enabling the body to choose between shuttling 'energy' towards accrual
      of a particular tissue (e.g. bone vs. fat) and this trait likely has a genetic component.
      This genetic component may be embedded in fat storage capacity evolved from gene by
      environment interactions that promote thrift, particularly conserved in some populations.
      Although genetic background plays a role, it not known whether there is a relationship
      between genetic background, known candidate genes or candidate pathways and environmental
      contributors (e.g. diet) that impact body composition trajectory. Of central importance to
      our understanding of early fat mass accumulation in health disparities are the mechanisms
      that lead to chronic disease progression.

      It is likely that variations within candidate genes may have a differential impact on
      individuals based on their genetic background. It is also probable that body composition is
      influenced by many genes, often within the same metabolic pathways, with small individual
      effects. These genes may not be significantly associated individually, but when examined as a
      unit (in a candidate pathway or gene-gene interaction framework) the association becomes
      significant. Further, children's early environmental exposures (e.g. diet) may interact with
      both genetic background and variations in candidate genes along resulting in alterations in
      body composition that predispose HA to excess fat accumulation throughout the lifecourse. To
      that end, the following specific aims will be evaluated:

      Aim 1. To examine the associations between genetic admixture and body composition in children
      aged 3-7 years after controlling for dietary intake.

        1. Hypothesis 1.1: There is a direct association between Amerindian admixture and fat mass
           and in inverse association between Amerindian admixture and bone mass.

        2. Hypothesis 1.2: There is a direct association between energy intake and fat accumulation
           and the relationship will be particularly evident in individuals with a greater
           proportion of Amerindian admixture.

      Aim 2. To examine the associations between genetic admixture and bone marrow fat in children
      aged 3-7 years after controlling for dietary intake.

        1. Hypothesis 2.1: There is a direct association between Amerindian admixture and bone
           marrow fat.

        2. Hypothesis 2.2: There is a direct association between energy intake and fat accumulation
           in bone marrow and the relationship will be particularly evident in individuals with a
           greater proportion of Amerindian admixture.

      Aim 3. To examine the relationship between variation in candidate genes and pathways and
      Amerindian admixture controlling for dietary intake.

      a. Hypothesis 3.1: Amerindian admixture will be associated with variations in candidate genes
      and pathways known to be associated with fat accumulation.
    


Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Participants will be healthy children self-identifed as Hispanic American aged 3 to seven
        years
      
Biospecimen description: 
      Samples will be labeled with the study protocol number, a unique identifier, and the date of
      collection.

      Specimens will be obtained by the nursing staff at the PCIR. The PCIR processing lab will
      process the samples, which will then be stored in a locked freezer at -80oC in the restricted
      access CNRU Metabolism Core lab (WEBB 337).
    
Keywords: nutrigenomics; admixture; Hispanic American; body composition; Association of diet and body composition; Association between genes and body composition; Association between gen by diet interaction and body composition