Cargando…

A genome-wide association study of serum uric acid in African Americans

BACKGROUND: Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI), sex, and multiple complex diseases including gout, hypertension (HTN), renal disease, and type 2 diabetes (T2D). Multiple genome-wide association studies (GWAS) in individuals...

Descripción completa

Detalles Bibliográficos
Autores principales: Charles, Bashira A, Shriner, Daniel, Doumatey, Ayo, Chen, Guanjie, Zhou, Jie, Huang, Hanxia, Herbert, Alan, Gerry, Norman P, Christman, Michael F, Adeyemo, Adebowale, Rotimi, Charles N
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045279/
https://www.ncbi.nlm.nih.gov/pubmed/21294900
http://dx.doi.org/10.1186/1755-8794-4-17
_version_ 1782198800956260352
author Charles, Bashira A
Shriner, Daniel
Doumatey, Ayo
Chen, Guanjie
Zhou, Jie
Huang, Hanxia
Herbert, Alan
Gerry, Norman P
Christman, Michael F
Adeyemo, Adebowale
Rotimi, Charles N
author_facet Charles, Bashira A
Shriner, Daniel
Doumatey, Ayo
Chen, Guanjie
Zhou, Jie
Huang, Hanxia
Herbert, Alan
Gerry, Norman P
Christman, Michael F
Adeyemo, Adebowale
Rotimi, Charles N
author_sort Charles, Bashira A
collection PubMed
description BACKGROUND: Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI), sex, and multiple complex diseases including gout, hypertension (HTN), renal disease, and type 2 diabetes (T2D). Multiple genome-wide association studies (GWAS) in individuals of European ancestry (EA) have reported associations between serum uric acid levels (SUAL) and specific genomic loci. The purposes of this study were: 1) to replicate major signals reported in EA populations; and 2) to use the weak LD pattern in African ancestry population to better localize (fine-map) reported loci and 3) to explore the identification of novel findings cognizant of the moderate sample size. METHODS: African American (AA) participants (n = 1,017) from the Howard University Family Study were included in this study. Genotyping was performed using the Affymetrix(® )Genome-wide Human SNP Array 6.0. Imputation was performed using MACH and the HapMap reference panels for CEU and YRI. A total of 2,400,542 single nucleotide polymorphisms (SNPs) were assessed for association with serum uric acid under the additive genetic model with adjustment for age, sex, BMI, glomerular filtration rate, HTN, T2D, and the top two principal components identified in the assessment of admixture and population stratification. RESULTS: Four variants in the gene SLC2A9 achieved genome-wide significance for association with SUAL (p-values ranging from 8.88 × 10(-9 )to 1.38 × 10(-9)). Fine-mapping of the SLC2A9 signals identified a 263 kb interval of linkage disequilibrium in the HapMap CEU sample. This interval was reduced to 37 kb in our AA and the HapMap YRI samples. CONCLUSIONS: The most strongly associated locus for SUAL in EA populations was also the most strongly associated locus in this AA sample. This finding provides evidence for the role of SLC2A9 in uric acid metabolism across human populations. Additionally, our findings demonstrate the utility of following-up EA populations GWAS signals in African-ancestry populations with weaker linkage disequilibrium.
format Text
id pubmed-3045279
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-30452792011-02-26 A genome-wide association study of serum uric acid in African Americans Charles, Bashira A Shriner, Daniel Doumatey, Ayo Chen, Guanjie Zhou, Jie Huang, Hanxia Herbert, Alan Gerry, Norman P Christman, Michael F Adeyemo, Adebowale Rotimi, Charles N BMC Med Genomics Research Article BACKGROUND: Uric acid is the primary byproduct of purine metabolism. Hyperuricemia is associated with body mass index (BMI), sex, and multiple complex diseases including gout, hypertension (HTN), renal disease, and type 2 diabetes (T2D). Multiple genome-wide association studies (GWAS) in individuals of European ancestry (EA) have reported associations between serum uric acid levels (SUAL) and specific genomic loci. The purposes of this study were: 1) to replicate major signals reported in EA populations; and 2) to use the weak LD pattern in African ancestry population to better localize (fine-map) reported loci and 3) to explore the identification of novel findings cognizant of the moderate sample size. METHODS: African American (AA) participants (n = 1,017) from the Howard University Family Study were included in this study. Genotyping was performed using the Affymetrix(® )Genome-wide Human SNP Array 6.0. Imputation was performed using MACH and the HapMap reference panels for CEU and YRI. A total of 2,400,542 single nucleotide polymorphisms (SNPs) were assessed for association with serum uric acid under the additive genetic model with adjustment for age, sex, BMI, glomerular filtration rate, HTN, T2D, and the top two principal components identified in the assessment of admixture and population stratification. RESULTS: Four variants in the gene SLC2A9 achieved genome-wide significance for association with SUAL (p-values ranging from 8.88 × 10(-9 )to 1.38 × 10(-9)). Fine-mapping of the SLC2A9 signals identified a 263 kb interval of linkage disequilibrium in the HapMap CEU sample. This interval was reduced to 37 kb in our AA and the HapMap YRI samples. CONCLUSIONS: The most strongly associated locus for SUAL in EA populations was also the most strongly associated locus in this AA sample. This finding provides evidence for the role of SLC2A9 in uric acid metabolism across human populations. Additionally, our findings demonstrate the utility of following-up EA populations GWAS signals in African-ancestry populations with weaker linkage disequilibrium. BioMed Central 2011-02-04 /pmc/articles/PMC3045279/ /pubmed/21294900 http://dx.doi.org/10.1186/1755-8794-4-17 Text en Copyright ©2011 Charles et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Charles, Bashira A
Shriner, Daniel
Doumatey, Ayo
Chen, Guanjie
Zhou, Jie
Huang, Hanxia
Herbert, Alan
Gerry, Norman P
Christman, Michael F
Adeyemo, Adebowale
Rotimi, Charles N
A genome-wide association study of serum uric acid in African Americans
title A genome-wide association study of serum uric acid in African Americans
title_full A genome-wide association study of serum uric acid in African Americans
title_fullStr A genome-wide association study of serum uric acid in African Americans
title_full_unstemmed A genome-wide association study of serum uric acid in African Americans
title_short A genome-wide association study of serum uric acid in African Americans
title_sort genome-wide association study of serum uric acid in african americans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3045279/
https://www.ncbi.nlm.nih.gov/pubmed/21294900
http://dx.doi.org/10.1186/1755-8794-4-17
work_keys_str_mv AT charlesbashiraa agenomewideassociationstudyofserumuricacidinafricanamericans
AT shrinerdaniel agenomewideassociationstudyofserumuricacidinafricanamericans
AT doumateyayo agenomewideassociationstudyofserumuricacidinafricanamericans
AT chenguanjie agenomewideassociationstudyofserumuricacidinafricanamericans
AT zhoujie agenomewideassociationstudyofserumuricacidinafricanamericans
AT huanghanxia agenomewideassociationstudyofserumuricacidinafricanamericans
AT herbertalan agenomewideassociationstudyofserumuricacidinafricanamericans
AT gerrynormanp agenomewideassociationstudyofserumuricacidinafricanamericans
AT christmanmichaelf agenomewideassociationstudyofserumuricacidinafricanamericans
AT adeyemoadebowale agenomewideassociationstudyofserumuricacidinafricanamericans
AT rotimicharlesn agenomewideassociationstudyofserumuricacidinafricanamericans
AT charlesbashiraa genomewideassociationstudyofserumuricacidinafricanamericans
AT shrinerdaniel genomewideassociationstudyofserumuricacidinafricanamericans
AT doumateyayo genomewideassociationstudyofserumuricacidinafricanamericans
AT chenguanjie genomewideassociationstudyofserumuricacidinafricanamericans
AT zhoujie genomewideassociationstudyofserumuricacidinafricanamericans
AT huanghanxia genomewideassociationstudyofserumuricacidinafricanamericans
AT herbertalan genomewideassociationstudyofserumuricacidinafricanamericans
AT gerrynormanp genomewideassociationstudyofserumuricacidinafricanamericans
AT christmanmichaelf genomewideassociationstudyofserumuricacidinafricanamericans
AT adeyemoadebowale genomewideassociationstudyofserumuricacidinafricanamericans
AT rotimicharlesn genomewideassociationstudyofserumuricacidinafricanamericans