Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations.
<h4>Background</h4>Liver disease is any condition that causes liver damage and inflammation and may likely affect the function of the liver. Vital biochemical screening tools that can be used to evaluate the health of the liver and help diagnose, prevent, monitor, and control the develop...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2023-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0280344&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849469819607318528 |
|---|---|
| author | Chisom Soremekun Tafadzwa Machipisa Opeyemi Soremekun Fraser Pirie Nashiru Oyekanmi Ayesha A Motala Tinashe Chikowore Segun Fatumo |
| author_facet | Chisom Soremekun Tafadzwa Machipisa Opeyemi Soremekun Fraser Pirie Nashiru Oyekanmi Ayesha A Motala Tinashe Chikowore Segun Fatumo |
| author_sort | Chisom Soremekun |
| collection | DOAJ |
| description | <h4>Background</h4>Liver disease is any condition that causes liver damage and inflammation and may likely affect the function of the liver. Vital biochemical screening tools that can be used to evaluate the health of the liver and help diagnose, prevent, monitor, and control the development of liver disease are known as liver function tests (LFT). LFTs are performed to estimate the level of liver biomarkers in the blood. Several factors are associated with differences in concentration levels of LFTs in individuals, such as genetic and environmental factors. The aim of our study was to identify genetic loci associated with liver biomarker levels with a shared genetic basis in continental Africans, using a multivariate genome-wide association study (GWAS) approach.<h4>Methods</h4>We used two distinct African populations, the Ugandan Genome Resource (UGR = 6,407) and South African Zulu cohort (SZC = 2,598). The six LFTs used in our analysis were: aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, and albumin. A multivariate GWAS of LFTs was conducted using the exact linear mixed model (mvLMM) approach implemented in GEMMA and the resulting P-values were presented in Manhattan and quantile-quantile (QQ) plots. First, we attempted to replicate the findings of the UGR cohort in SZC. Secondly, given that the genetic architecture of UGR is different from that of SZC, we further undertook similar analysis in the SZC and discussed the results separately.<h4>Results</h4>A total of 59 SNPs reached genome-wide significance (P = 5x10-8) in the UGR cohort and with 13 SNPs successfully replicated in SZC. These included a novel lead SNP near the RHPN1 locus (lead SNP rs374279268, P-value = 4.79x10-9, Effect Allele Frequency (EAF) = 0.989) and a lead SNP at the RGS11 locus (lead SNP rs148110594, P-value = 2.34x10-8, EAF = 0.928). 17 SNPs were significant in the SZC, while all the SNPs fall within a signal on chromosome 2, rs1976391 mapped to UGT1A was identified as the lead SNP within this region.<h4>Conclusions</h4>Using multivariate GWAS method improves the power to detect novel genotype-phenotype associations for liver functions not found with the standard univariate GWAS in the same dataset. |
| format | Article |
| id | doaj-art-cdd324924d5043c1843dbf0998d5fc50 |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2023-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-cdd324924d5043c1843dbf0998d5fc502025-08-20T03:25:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032023-01-01182e028034410.1371/journal.pone.0280344Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations.Chisom SoremekunTafadzwa MachipisaOpeyemi SoremekunFraser PirieNashiru OyekanmiAyesha A MotalaTinashe ChikoworeSegun Fatumo<h4>Background</h4>Liver disease is any condition that causes liver damage and inflammation and may likely affect the function of the liver. Vital biochemical screening tools that can be used to evaluate the health of the liver and help diagnose, prevent, monitor, and control the development of liver disease are known as liver function tests (LFT). LFTs are performed to estimate the level of liver biomarkers in the blood. Several factors are associated with differences in concentration levels of LFTs in individuals, such as genetic and environmental factors. The aim of our study was to identify genetic loci associated with liver biomarker levels with a shared genetic basis in continental Africans, using a multivariate genome-wide association study (GWAS) approach.<h4>Methods</h4>We used two distinct African populations, the Ugandan Genome Resource (UGR = 6,407) and South African Zulu cohort (SZC = 2,598). The six LFTs used in our analysis were: aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), total bilirubin, and albumin. A multivariate GWAS of LFTs was conducted using the exact linear mixed model (mvLMM) approach implemented in GEMMA and the resulting P-values were presented in Manhattan and quantile-quantile (QQ) plots. First, we attempted to replicate the findings of the UGR cohort in SZC. Secondly, given that the genetic architecture of UGR is different from that of SZC, we further undertook similar analysis in the SZC and discussed the results separately.<h4>Results</h4>A total of 59 SNPs reached genome-wide significance (P = 5x10-8) in the UGR cohort and with 13 SNPs successfully replicated in SZC. These included a novel lead SNP near the RHPN1 locus (lead SNP rs374279268, P-value = 4.79x10-9, Effect Allele Frequency (EAF) = 0.989) and a lead SNP at the RGS11 locus (lead SNP rs148110594, P-value = 2.34x10-8, EAF = 0.928). 17 SNPs were significant in the SZC, while all the SNPs fall within a signal on chromosome 2, rs1976391 mapped to UGT1A was identified as the lead SNP within this region.<h4>Conclusions</h4>Using multivariate GWAS method improves the power to detect novel genotype-phenotype associations for liver functions not found with the standard univariate GWAS in the same dataset.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0280344&type=printable |
| spellingShingle | Chisom Soremekun Tafadzwa Machipisa Opeyemi Soremekun Fraser Pirie Nashiru Oyekanmi Ayesha A Motala Tinashe Chikowore Segun Fatumo Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations. PLoS ONE |
| title | Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations. |
| title_full | Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations. |
| title_fullStr | Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations. |
| title_full_unstemmed | Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations. |
| title_short | Multivariate GWAS analysis reveals loci associated with liver functions in continental African populations. |
| title_sort | multivariate gwas analysis reveals loci associated with liver functions in continental african populations |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0280344&type=printable |
| work_keys_str_mv | AT chisomsoremekun multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations AT tafadzwamachipisa multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations AT opeyemisoremekun multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations AT fraserpirie multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations AT nashiruoyekanmi multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations AT ayeshaamotala multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations AT tinashechikowore multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations AT segunfatumo multivariategwasanalysisrevealslociassociatedwithliverfunctionsincontinentalafricanpopulations |