Fine mapping and identification of serum urate loci in American Indians: The Strong Heart Family Study.
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ABSTRACT:
SUBMITTER: Chittoor G
PROVIDER: S-EPMC6884539 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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Fine mapping and identification of serum urate loci in American Indians: The Strong Heart Family Study.
Chittoor Geetha G Haack Karin K Balakrishnan Poojitha P Bizon Christopher C Laston Sandra S Best Lyle G LG MacCluer Jean W JW North Kari E KE Umans Jason G JG Franceschini Nora N Prasad Gauri G Macias-Kauffer Luis L Villarreal-Molina Teresa T Bharadwaj Dwaipayan D Canizales-Quinteros Samuel S Navas-Acien Ana A Cole Shelley A SA Voruganti V S VS
Scientific reports 20191129 1
While studies have reported genetic loci affecting serum urate (SU) concentrations, few studies have been conducted in minority populations. Our objective for this study was to identify genetic loci regulating SU in a multigenerational family-based cohort of American Indians, the Strong Heart Family Study (SHFS). We genotyped 162,718 single nucleotide polymorphisms (SNPs) in 2000 SHFS participants using an Illumina MetaboChip array. A genome-wide association analysis of SU was conducted using me ...[more]
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Project description:ObjectiveTo identify genetic variation influencing serum bilirubin levels in American Indians, we performed genome-wide screening and association analyses in the Strong Heart Family Study. Bilirubin is an endogenous antioxidant that has demonstrated an inverse relationship with cardiovascular disease. Genetic variation within the promoter region of uridine diphosphate glucuronosyltransferase (UGT1A1) on chromosome 2q has been associated with elevated serum bilirubin levels in European populations. However, no study has investigated the UGT1A1 promoter in American Indians.MethodsStatistical analyses were carried out with 3,484 participants aged 14 to 93 years recruited from three geographic areas in the United States; Arizona, Oklahoma, and North and South Dakota.ResultsVariance components linkage analysis detected a quantitative trait locus (QTL) for bilirubin on chromosome 2q in the combined centers (LOD = 6.61, P = 4.24 × 10⁻⁶) and in Oklahoma (LOD = 5.65, P = 4.57 24 × 10⁻⁵). Genetic association of the UGT1A1 promoter polymorphism was significant for all geographic locations. After adjustment using conditional linkage for UGT1A1 promoter variance, the linkage signal dropped to 1.10 in the combined sample and to 3.32 (P = 0.02) in Oklahoma, indicating this polymorphism is not completely responsible for the linkage signal in American Indians. We also detected suggestive linkage signals in the Dakotas on chromosome 10p12 (LOD = 2.18) and in the combined centers (LOD = 2.24) on chromosome 10q21.ConclusionsReplication of a serum bilirubin QTL on chromosome 2q in American Indians implicates UGT1A1 but further genotyping is warranted to identify additional causative polymorphisms. Evidence also supports a potential novel locus for bilirubin on chromosome 10.
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