A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals
Abstract Serum bilirubin is associated with several clinical outcomes, including hypertension, type 2 diabetes (T2D), and drug metabolism. Here, we describe findings from our genome-wide association studies (GWAS) of serum (TBIL) using a generalized linear mixed model in West Africans (n = 1127), wi...
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Nature Portfolio
2021
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oai:doaj.org-article:054ecbf06a9d4a039ab5149e2fa661c42021-12-02T15:03:08ZA UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals10.1038/s41525-021-00208-62056-7944https://doaj.org/article/054ecbf06a9d4a039ab5149e2fa661c42021-06-01T00:00:00Zhttps://doi.org/10.1038/s41525-021-00208-6https://doaj.org/toc/2056-7944Abstract Serum bilirubin is associated with several clinical outcomes, including hypertension, type 2 diabetes (T2D), and drug metabolism. Here, we describe findings from our genome-wide association studies (GWAS) of serum (TBIL) using a generalized linear mixed model in West Africans (n = 1127), with adjustment for age, sex, body mass index, T2D, significant principal components of population structure, and cryptic relatedness. Genome-wide conditional analysis and CAVIARBF were used to fine map significant loci. The causal effect of TBIL on hypertension was assessed by Mendelian randomization (MR) using the GWAS findings as instrumental variables (IVs) in African Americans (n = 3,067). The SNP rs887829 (UGT1A1) was significantly associated with TBIL levels (effect allele (T) frequency = 0.49, β (SE) = 0.59 (0.04), p = 9.13 × 10−54). Genome-wide conditional analysis and regional fine mapping pointed to rs887829 as a possible causal variant with a posterior inclusion probability of 0.99. The T allele of rs887829 is associated with lower hepatic expression of UGT1A1. Using rs887829 as an IV, two-stage least-squares MR showed a causal effect of bilirubin on hypertension (β = −0.76, 95% CI [−1.52, −0.01], p = 0.0459). Our finding confirms that UGT1A1 influences bilirubin levels. Notably, lower TBIL is causally associated with the increased risk of hypertension.Guanjie ChenAdebowale AdeyemoJie ZhouAyo P. DoumateyAmy R. BentleyKenneth EkoruDaniel ShrinerCharles N. RotimiNature PortfolioarticleMedicineRGeneticsQH426-470ENnpj Genomic Medicine, Vol 6, Iss 1, Pp 1-6 (2021) |
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Medicine R Genetics QH426-470 |
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Medicine R Genetics QH426-470 Guanjie Chen Adebowale Adeyemo Jie Zhou Ayo P. Doumatey Amy R. Bentley Kenneth Ekoru Daniel Shriner Charles N. Rotimi A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals |
| description |
Abstract Serum bilirubin is associated with several clinical outcomes, including hypertension, type 2 diabetes (T2D), and drug metabolism. Here, we describe findings from our genome-wide association studies (GWAS) of serum (TBIL) using a generalized linear mixed model in West Africans (n = 1127), with adjustment for age, sex, body mass index, T2D, significant principal components of population structure, and cryptic relatedness. Genome-wide conditional analysis and CAVIARBF were used to fine map significant loci. The causal effect of TBIL on hypertension was assessed by Mendelian randomization (MR) using the GWAS findings as instrumental variables (IVs) in African Americans (n = 3,067). The SNP rs887829 (UGT1A1) was significantly associated with TBIL levels (effect allele (T) frequency = 0.49, β (SE) = 0.59 (0.04), p = 9.13 × 10−54). Genome-wide conditional analysis and regional fine mapping pointed to rs887829 as a possible causal variant with a posterior inclusion probability of 0.99. The T allele of rs887829 is associated with lower hepatic expression of UGT1A1. Using rs887829 as an IV, two-stage least-squares MR showed a causal effect of bilirubin on hypertension (β = −0.76, 95% CI [−1.52, −0.01], p = 0.0459). Our finding confirms that UGT1A1 influences bilirubin levels. Notably, lower TBIL is causally associated with the increased risk of hypertension. |
| format |
article |
| author |
Guanjie Chen Adebowale Adeyemo Jie Zhou Ayo P. Doumatey Amy R. Bentley Kenneth Ekoru Daniel Shriner Charles N. Rotimi |
| author_facet |
Guanjie Chen Adebowale Adeyemo Jie Zhou Ayo P. Doumatey Amy R. Bentley Kenneth Ekoru Daniel Shriner Charles N. Rotimi |
| author_sort |
Guanjie Chen |
| title |
A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals |
| title_short |
A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals |
| title_full |
A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals |
| title_fullStr |
A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals |
| title_full_unstemmed |
A UGT1A1 variant is associated with serum total bilirubin levels, which are causal for hypertension in African-ancestry individuals |
| title_sort |
ugt1a1 variant is associated with serum total bilirubin levels, which are causal for hypertension in african-ancestry individuals |
| publisher |
Nature Portfolio |
| publishDate |
2021 |
| url |
https://doaj.org/article/054ecbf06a9d4a039ab5149e2fa661c4 |
| work_keys_str_mv |
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