Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility.
Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,08...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3428296?pdf=render |
| _version_ | 1818683985112334336 |
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| author | Indra Adrianto Chee Paul Lin Jessica J Hale Albert M Levin Indrani Datta Ryan Parker Adam Adler Jennifer A Kelly Kenneth M Kaufman Christopher J Lessard Kathy L Moser Robert P Kimberly John B Harley Michael C Iannuzzi Benjamin A Rybicki Courtney G Montgomery |
| author_facet | Indra Adrianto Chee Paul Lin Jessica J Hale Albert M Levin Indrani Datta Ryan Parker Adam Adler Jennifer A Kelly Kenneth M Kaufman Christopher J Lessard Kathy L Moser Robert P Kimberly John B Harley Michael C Iannuzzi Benjamin A Rybicki Courtney G Montgomery |
| author_sort | Indra Adrianto |
| collection | DOAJ |
| description | Sarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, NOTCH4, that reached genome-wide significance in the combined AA samples (rs715299, P(AA-meta) = 6.51 × 10(-10)) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within HLA-DRA, HLA-DRB5, HLA-DRB1, BTNL2, and ANXA11 in both our AA and EA datasets. We also confirmed significant associations to the previously reported HLA-C and HLA-B regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases. |
| first_indexed | 2024-12-17T10:43:26Z |
| format | Article |
| id | doaj.art-cd17fb0999dc43b68e078bac4cdc10ad |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T10:43:26Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cd17fb0999dc43b68e078bac4cdc10ad2022-12-21T21:52:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4390710.1371/journal.pone.0043907Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility.Indra AdriantoChee Paul LinJessica J HaleAlbert M LevinIndrani DattaRyan ParkerAdam AdlerJennifer A KellyKenneth M KaufmanChristopher J LessardKathy L MoserRobert P KimberlyJohn B HarleyMichael C IannuzziBenjamin A RybickiCourtney G MontgomerySarcoidosis is a systemic inflammatory disease characterized by the formation of granulomas in affected organs. Genome-wide association studies (GWASs) of this disease have been conducted only in European population. We present the first sarcoidosis GWAS in African Americans (AAs, 818 cases and 1,088 related controls) followed by replication in independent sets of AAs (455 cases and 557 controls) and European Americans (EAs, 442 cases and 2,284 controls). We evaluated >6 million SNPs either genotyped using the Illumina Omni1-Quad array or imputed from the 1000 Genomes Project data. We identified a novel sarcoidosis-associated locus, NOTCH4, that reached genome-wide significance in the combined AA samples (rs715299, P(AA-meta) = 6.51 × 10(-10)) and demonstrated the independence of this locus from others in the MHC region in the same sample. We replicated previous European GWAS associations within HLA-DRA, HLA-DRB5, HLA-DRB1, BTNL2, and ANXA11 in both our AA and EA datasets. We also confirmed significant associations to the previously reported HLA-C and HLA-B regions in the EA but not AA samples. We further identified suggestive associations with several other genes previously reported in lung or inflammatory diseases.http://europepmc.org/articles/PMC3428296?pdf=render |
| spellingShingle | Indra Adrianto Chee Paul Lin Jessica J Hale Albert M Levin Indrani Datta Ryan Parker Adam Adler Jennifer A Kelly Kenneth M Kaufman Christopher J Lessard Kathy L Moser Robert P Kimberly John B Harley Michael C Iannuzzi Benjamin A Rybicki Courtney G Montgomery Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. PLoS ONE |
| title | Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. |
| title_full | Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. |
| title_fullStr | Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. |
| title_full_unstemmed | Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. |
| title_short | Genome-wide association study of African and European Americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility. |
| title_sort | genome wide association study of african and european americans implicates multiple shared and ethnic specific loci in sarcoidosis susceptibility |
| url | http://europepmc.org/articles/PMC3428296?pdf=render |
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