Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study
Variations in lipid levels are attributed partly to genetic factors. Genome-wide association studies (GWASs) mainly performed in European, African American and Asian cohorts have identified variants associated with LDL-C, HDL-C, total cholesterol (TC) and triglycerides (TG), but few studies have bee...
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Frontiers Media S.A.
2020-10-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2020.456661/full |
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| author | Godfred Agongo Godfred Agongo Godfred Agongo Lucas Amenga-Etego Lucas Amenga-Etego Engelbert A. Nonterah Engelbert A. Nonterah Cornelius Debpuur Ananyo Choudhury Amy R. Bentley Abraham R. Oduro Charles N. Rotimi Nigel J. Crowther Michèle Ramsay Michèle Ramsay AWI-Gen and H3Africa H3Africa |
| author_facet | Godfred Agongo Godfred Agongo Godfred Agongo Lucas Amenga-Etego Lucas Amenga-Etego Engelbert A. Nonterah Engelbert A. Nonterah Cornelius Debpuur Ananyo Choudhury Amy R. Bentley Abraham R. Oduro Charles N. Rotimi Nigel J. Crowther Michèle Ramsay Michèle Ramsay AWI-Gen and H3Africa H3Africa |
| author_sort | Godfred Agongo |
| collection | DOAJ |
| description | Variations in lipid levels are attributed partly to genetic factors. Genome-wide association studies (GWASs) mainly performed in European, African American and Asian cohorts have identified variants associated with LDL-C, HDL-C, total cholesterol (TC) and triglycerides (TG), but few studies have been performed in sub-Saharan Africans. This study evaluated the effect of single nucleotide variants (SNVs) in eight candidate loci (ABCA1, LCAT, LPL, PON1, CETP, PCSK9, MVK, and MMAB) on lipid levels among 1855 Ghanaian adults. All lipid levels were measured directly using an automated analyser. DNA was extracted and genotyped using the H3Africa SNV array. Linear regression models were used to test the association between SNVs and log-transformed lipid levels, adjusting for sex, age and waist circumference. In addition Bonferroni correction was performed to account for multiple testing. Several variants of CETP, LCAT, PCSK9, and PON1 (MAF > 0.05) were associated with HDL-C, LDL-C and TC levels at p < 0.05. The lead variants for association with HDL-C were rs17231520 in CETP (β = 0.139, p < 0.0001) and rs1109166 in LCAT (β = −0.044, p = 0.028). Lower LDL-C levels were associated with an intronic variant in PCSK9 (rs11806638 [β = −0.055, p = 0.027]) and increased TC was associated with a variant in PON1 (rs854558 [β = 0.040, p = 0.020]). In silico functional analyses indicated that these variants likely influence gene function through their effect on gene transcription. We replicated a strong association between CETP variants and HDL-C and between PCSK9 variant and LDL-C in West Africans, with two potentially functional variants and identified three novel variants in linkage disequilibrium in PON1 which were associated with increasing TC levels in Ghanaians. |
| first_indexed | 2024-04-13T23:54:57Z |
| format | Article |
| id | doaj.art-dda133a5d5904473a385ed6212011d05 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-13T23:54:57Z |
| publishDate | 2020-10-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-dda133a5d5904473a385ed6212011d052022-12-22T02:23:55ZengFrontiers Media S.A.Frontiers in Genetics1664-80212020-10-011110.3389/fgene.2020.456661456661Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-StudyGodfred Agongo0Godfred Agongo1Godfred Agongo2Lucas Amenga-Etego3Lucas Amenga-Etego4Engelbert A. Nonterah5Engelbert A. Nonterah6Cornelius Debpuur7Ananyo Choudhury8Amy R. Bentley9Abraham R. Oduro10Charles N. Rotimi11Nigel J. Crowther12Michèle Ramsay13Michèle Ramsay14AWI-Gen and H3Africa H3AfricaNavrongo Health Research Centre, Navrongo, GhanaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaDivision of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaNavrongo Health Research Centre, Navrongo, GhanaWest African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, University of Ghana, Legon, GhanaNavrongo Health Research Centre, Navrongo, GhanaJulius Global Health, Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht University, Utrecht, NetherlandsNavrongo Health Research Centre, Navrongo, GhanaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesNavrongo Health Research Centre, Navrongo, GhanaCenter for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United StatesDepartment of Chemical Pathology, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaSydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaDivision of Human Genetics, National Health Laboratory Service and School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South AfricaVariations in lipid levels are attributed partly to genetic factors. Genome-wide association studies (GWASs) mainly performed in European, African American and Asian cohorts have identified variants associated with LDL-C, HDL-C, total cholesterol (TC) and triglycerides (TG), but few studies have been performed in sub-Saharan Africans. This study evaluated the effect of single nucleotide variants (SNVs) in eight candidate loci (ABCA1, LCAT, LPL, PON1, CETP, PCSK9, MVK, and MMAB) on lipid levels among 1855 Ghanaian adults. All lipid levels were measured directly using an automated analyser. DNA was extracted and genotyped using the H3Africa SNV array. Linear regression models were used to test the association between SNVs and log-transformed lipid levels, adjusting for sex, age and waist circumference. In addition Bonferroni correction was performed to account for multiple testing. Several variants of CETP, LCAT, PCSK9, and PON1 (MAF > 0.05) were associated with HDL-C, LDL-C and TC levels at p < 0.05. The lead variants for association with HDL-C were rs17231520 in CETP (β = 0.139, p < 0.0001) and rs1109166 in LCAT (β = −0.044, p = 0.028). Lower LDL-C levels were associated with an intronic variant in PCSK9 (rs11806638 [β = −0.055, p = 0.027]) and increased TC was associated with a variant in PON1 (rs854558 [β = 0.040, p = 0.020]). In silico functional analyses indicated that these variants likely influence gene function through their effect on gene transcription. We replicated a strong association between CETP variants and HDL-C and between PCSK9 variant and LDL-C in West Africans, with two potentially functional variants and identified three novel variants in linkage disequilibrium in PON1 which were associated with increasing TC levels in Ghanaians.https://www.frontiersin.org/articles/10.3389/fgene.2020.456661/fullcandidate genelipidsingle nucleotide variantGhanaiansAWI-Gen |
| spellingShingle | Godfred Agongo Godfred Agongo Godfred Agongo Lucas Amenga-Etego Lucas Amenga-Etego Engelbert A. Nonterah Engelbert A. Nonterah Cornelius Debpuur Ananyo Choudhury Amy R. Bentley Abraham R. Oduro Charles N. Rotimi Nigel J. Crowther Michèle Ramsay Michèle Ramsay AWI-Gen and H3Africa H3Africa Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study Frontiers in Genetics candidate gene lipid single nucleotide variant Ghanaians AWI-Gen |
| title | Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study |
| title_full | Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study |
| title_fullStr | Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study |
| title_full_unstemmed | Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study |
| title_short | Candidate Gene Analysis Reveals Strong Association of CETP Variants With High Density Lipoprotein Cholesterol and PCSK9 Variants With Low Density Lipoprotein Cholesterol in Ghanaian Adults: An AWI-Gen Sub-Study |
| title_sort | candidate gene analysis reveals strong association of cetp variants with high density lipoprotein cholesterol and pcsk9 variants with low density lipoprotein cholesterol in ghanaian adults an awi gen sub study |
| topic | candidate gene lipid single nucleotide variant Ghanaians AWI-Gen |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2020.456661/full |
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