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Multilocus genetic associations with obesity outcomes in Hispanic and non-Hispanic whites using a principal components regression approach: the San Luis Valley Diabetes Study

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dc.contributor.authorBooth-Kalajian, Andrea D., author
dc.contributor.authorNelson, Tracy, advisor
dc.contributor.authorMelby, Chris, advisor
dc.contributor.authorHokanson, John, committee member
dc.contributor.authorPeel, Jennifer, committee member
dc.contributor.authorBellows, Laura, committee member
dc.date.accessioned2007-01-03T04:56:36Z
dc.date.available2007-01-03T04:56:36Z
dc.date.issued2013
dc.description.abstractIntroduction: The overweight and obesity crisis in America has reached alarming rates with little progress of reversing the trend, despite much effort. Heritability has been estimated at up to 70%, though it is still unclear how genetics respond to environmental pressures. Evaluating groups of genes that are known to influence metabolic pathways has given some insight into the variation we see in body composition and prevalence of metabolic diseases. Methods: Data from the San Luis Valley Diabetes Study's third examination were utilized (1997-1998, n=837). One hundred seven single nucleotide polymorphisms (SNP) were selected from 22 genes that have previously been associated with obesity and type 2 diabetes (T2D) in a cohort of Hispanic and non-Hispanic white (NHW) individuals. Genetic data were reduced to a smaller set of derived factors using principal components analysis (PC). Associations were determined between factors and obesity outcomes. Results: Hispanics were more likely to have T2D than NHW (19% vs. 11%). Sample minor allele frequencies for 100 analyzable SNPs varied between the two groups with the minor alleles of rs8059937 (A2BP1) and rs6822807 (UCP1) being significantly more prevalent in Hispanics and rs11724758 (FABP2) and rs2239179 (VDR) significantly more prevalent in NHWs. SNP variance was redistributed into orthogonal components and 32 were retained for analysis, accounting for 77% of the total variance in genetic data. The combined genetic information increased predictive power of increases in body mass index (BMI) from the study baseline by 5.6% in Hispanics. Genetic data increased predictability of BMI and waist circumference (WC) in NHWs by 7.5% and 5.1%, respectively. Both groups had a significant increase in knowledge gained (18%) for the prevalence of T2D when genetic information was added to the base model. SNPs from UCP1 loaded strongly onto PC4, which was associated with BMI change in Hispanics and BMI, WC, and T2D in NHWs. PC7 represented SNPs from RBP4 and FABP2, which was associated with diabetes status in both groups. All obesity outcomes were associated with PC15 in Hispanics, symbolizing SNPs on the PPARD and RBP4 genes. NHWs showed additional associations with components having strong loadings from SNPs on multiple genes, including ADIPOQ, GC, VDR, PPARG, PPARGC1A, PPARD, UCP2, UCP3, and AlOX15. Conclusions: When combined together, multilocus genetic data show a larger influence on obesity outcomes than single polymorphisms alone. Base variations in UCP1, RBP4, and FABP2 gene sequences are associated with change in BMI and diabetes status in Hispanics and BMI, WC, and diabetes status in NHWs.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierBoothKalajian_colostate_0053N_11734.pdf
dc.identifier.urihttp://hdl.handle.net/10217/79010
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectprincipal components
dc.subjectobesity
dc.subjecttype 2 diabetes
dc.subjectgenetics
dc.subjectHispanics
dc.titleMultilocus genetic associations with obesity outcomes in Hispanic and non-Hispanic whites using a principal components regression approach: the San Luis Valley Diabetes Study
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineFood Science and Human Nutrition
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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