A genome-wide association study of hypertension and blood pressure in African Americans.
The evidence for the existence of genetic susceptibility variants for the common form of hypertension ("essential hypertension") remains weak and inconsistent. We sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Ameri...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-07-01
|
| Series: | PLoS Genetics |
| Online Access: | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000564&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850108065793179648 |
|---|---|
| author | Adebowale Adeyemo Norman Gerry Guanjie Chen Alan Herbert Ayo Doumatey Hanxia Huang Jie Zhou Kerrie Lashley Yuanxiu Chen Michael Christman Charles Rotimi |
| author_facet | Adebowale Adeyemo Norman Gerry Guanjie Chen Alan Herbert Ayo Doumatey Hanxia Huang Jie Zhou Kerrie Lashley Yuanxiu Chen Michael Christman Charles Rotimi |
| author_sort | Adebowale Adeyemo |
| collection | DOAJ |
| description | The evidence for the existence of genetic susceptibility variants for the common form of hypertension ("essential hypertension") remains weak and inconsistent. We sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases. Using a dense panel of over 800,000 SNPs in a discovery sample of 1,017 African Americans from the Washington, D.C., metropolitan region, we identified multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP (top scoring SNP rs1867226, p = 5.8 x 10(-7)) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1 x 10(-7)). We replicated some of the significant SNPs in a sample of West Africans. Pathway analysis revealed that genes harboring top-scoring variants cluster in pathways and networks of biologic relevance to hypertension and BP regulation. This is the first GWAS for hypertension and BP in an African American population. The findings suggests that, in addition to or in lieu of relying solely on replicated variants of moderate-to-large effect reaching genome-wide significance, pathway and network approaches may be useful in identifying and prioritizing candidate genes/loci for further experiments. |
| format | Article |
| id | doaj-art-20a7da60efcc42948501239fd86c819c |
| institution | OA Journals |
| issn | 1553-7390 1553-7404 |
| language | English |
| publishDate | 2009-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj-art-20a7da60efcc42948501239fd86c819c2025-08-20T02:38:27ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042009-07-0157e100056410.1371/journal.pgen.1000564A genome-wide association study of hypertension and blood pressure in African Americans.Adebowale AdeyemoNorman GerryGuanjie ChenAlan HerbertAyo DoumateyHanxia HuangJie ZhouKerrie LashleyYuanxiu ChenMichael ChristmanCharles RotimiThe evidence for the existence of genetic susceptibility variants for the common form of hypertension ("essential hypertension") remains weak and inconsistent. We sought genetic variants underlying blood pressure (BP) by conducting a genome-wide association study (GWAS) among African Americans, a population group in the United States that is disproportionately affected by hypertension and associated complications, including stroke and kidney diseases. Using a dense panel of over 800,000 SNPs in a discovery sample of 1,017 African Americans from the Washington, D.C., metropolitan region, we identified multiple SNPs reaching genome-wide significance for systolic BP in or near the genes: PMS1, SLC24A4, YWHA7, IPO7, and CACANA1H. Two of these genes, SLC24A4 (a sodium/potassium/calcium exchanger) and CACNA1H (a voltage-dependent calcium channel), are potential candidate genes for BP regulation and the latter is a drug target for a class of calcium channel blockers. No variant reached genome wide significance for association with diastolic BP (top scoring SNP rs1867226, p = 5.8 x 10(-7)) or with hypertension as a binary trait (top scoring SNP rs9791170, p = 5.1 x 10(-7)). We replicated some of the significant SNPs in a sample of West Africans. Pathway analysis revealed that genes harboring top-scoring variants cluster in pathways and networks of biologic relevance to hypertension and BP regulation. This is the first GWAS for hypertension and BP in an African American population. The findings suggests that, in addition to or in lieu of relying solely on replicated variants of moderate-to-large effect reaching genome-wide significance, pathway and network approaches may be useful in identifying and prioritizing candidate genes/loci for further experiments.https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000564&type=printable |
| spellingShingle | Adebowale Adeyemo Norman Gerry Guanjie Chen Alan Herbert Ayo Doumatey Hanxia Huang Jie Zhou Kerrie Lashley Yuanxiu Chen Michael Christman Charles Rotimi A genome-wide association study of hypertension and blood pressure in African Americans. PLoS Genetics |
| title | A genome-wide association study of hypertension and blood pressure in African Americans. |
| title_full | A genome-wide association study of hypertension and blood pressure in African Americans. |
| title_fullStr | A genome-wide association study of hypertension and blood pressure in African Americans. |
| title_full_unstemmed | A genome-wide association study of hypertension and blood pressure in African Americans. |
| title_short | A genome-wide association study of hypertension and blood pressure in African Americans. |
| title_sort | genome wide association study of hypertension and blood pressure in african americans |
| url | https://journals.plos.org/plosgenetics/article/file?id=10.1371/journal.pgen.1000564&type=printable |
| work_keys_str_mv | AT adebowaleadeyemo agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT normangerry agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT guanjiechen agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT alanherbert agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT ayodoumatey agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT hanxiahuang agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT jiezhou agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT kerrielashley agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT yuanxiuchen agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT michaelchristman agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT charlesrotimi agenomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT adebowaleadeyemo genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT normangerry genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT guanjiechen genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT alanherbert genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT ayodoumatey genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT hanxiahuang genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT jiezhou genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT kerrielashley genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT yuanxiuchen genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT michaelchristman genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans AT charlesrotimi genomewideassociationstudyofhypertensionandbloodpressureinafricanamericans |