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Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci
Genome-wide association studies (GWASs) have proven highly effective, identifying hundreds of associations across numerous complex diseases. These studies typically test hundreds of thousands of variations and identify hundreds of potential associations. However, to date, follow-up attempts have gen...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Oxford University Press
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816610/ https://www.ncbi.nlm.nih.gov/pubmed/20007504 http://dx.doi.org/10.1093/hmg/ddp542 |
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author | McCauley, Jacob L. Zuvich, Rebecca L. Beecham, Ashley H. De Jager, Philip L. Konidari, Ioanna Whitehead, Patrice L. Aubin, Cristin Ban, Maria Pobywajlo, Susan Briskin, Rebeccah Romano, Susan Aggarwal, Neelum T. Piccio, Laura McArdle, Wendy L. Strachan, David P. Evans, Denis Cross, Anne H. Cree, Bruce Rioux, John D. Barcellos, Lisa F. Ivinson, Adrian J. Compston, Alastair Hafler, David A. Hauser, Stephen L. Oksenberg, Jorge R. Sawcer, Stephen J. Pericak-Vance, Margaret A. Haines, Jonathan L. |
author_facet | McCauley, Jacob L. Zuvich, Rebecca L. Beecham, Ashley H. De Jager, Philip L. Konidari, Ioanna Whitehead, Patrice L. Aubin, Cristin Ban, Maria Pobywajlo, Susan Briskin, Rebeccah Romano, Susan Aggarwal, Neelum T. Piccio, Laura McArdle, Wendy L. Strachan, David P. Evans, Denis Cross, Anne H. Cree, Bruce Rioux, John D. Barcellos, Lisa F. Ivinson, Adrian J. Compston, Alastair Hafler, David A. Hauser, Stephen L. Oksenberg, Jorge R. Sawcer, Stephen J. Pericak-Vance, Margaret A. Haines, Jonathan L. |
collection | PubMed |
description | Genome-wide association studies (GWASs) have proven highly effective, identifying hundreds of associations across numerous complex diseases. These studies typically test hundreds of thousands of variations and identify hundreds of potential associations. However, to date, follow-up attempts have generally only concentrated on just the few most significant initial associations, leaving the majority of true associations in any GWAS study without replication. Here, we present a substantially more comprehensive follow-up of the first genome-wide association screen performed in multiple sclerosis (MS), a complex genetic disease with central nervous system inflammation. We genotyped approximately 30 000 single-nucleotide polymorphisms (SNPs) that demonstrated mild-to-moderate levels of significance (P ≤ 0.10) in the initial GWAS in an independent set of 1343 MS cases and 1379 controls. We further replicated several of the most significant findings in another independent data set of 2164 MS cases and 2016 controls. We find considerable evidence for a number of novel susceptibility loci including KIF21B [rs12122721, combined P = 6.56 × 10(−10), odds ratio (OR) = 1.22] and TMEM39A (rs1132200, P = 3.09 × 10(−8), OR = 1.24), both of which meet genome-wide significance. Both of these loci were overlooked in the initial replication, despite being among the top 3000 (∼1%) SNP hits in the original screen. |
format | Text |
id | pubmed-2816610 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-28166102010-02-05 Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci McCauley, Jacob L. Zuvich, Rebecca L. Beecham, Ashley H. De Jager, Philip L. Konidari, Ioanna Whitehead, Patrice L. Aubin, Cristin Ban, Maria Pobywajlo, Susan Briskin, Rebeccah Romano, Susan Aggarwal, Neelum T. Piccio, Laura McArdle, Wendy L. Strachan, David P. Evans, Denis Cross, Anne H. Cree, Bruce Rioux, John D. Barcellos, Lisa F. Ivinson, Adrian J. Compston, Alastair Hafler, David A. Hauser, Stephen L. Oksenberg, Jorge R. Sawcer, Stephen J. Pericak-Vance, Margaret A. Haines, Jonathan L. Hum Mol Genet Association Studies Articles Genome-wide association studies (GWASs) have proven highly effective, identifying hundreds of associations across numerous complex diseases. These studies typically test hundreds of thousands of variations and identify hundreds of potential associations. However, to date, follow-up attempts have generally only concentrated on just the few most significant initial associations, leaving the majority of true associations in any GWAS study without replication. Here, we present a substantially more comprehensive follow-up of the first genome-wide association screen performed in multiple sclerosis (MS), a complex genetic disease with central nervous system inflammation. We genotyped approximately 30 000 single-nucleotide polymorphisms (SNPs) that demonstrated mild-to-moderate levels of significance (P ≤ 0.10) in the initial GWAS in an independent set of 1343 MS cases and 1379 controls. We further replicated several of the most significant findings in another independent data set of 2164 MS cases and 2016 controls. We find considerable evidence for a number of novel susceptibility loci including KIF21B [rs12122721, combined P = 6.56 × 10(−10), odds ratio (OR) = 1.22] and TMEM39A (rs1132200, P = 3.09 × 10(−8), OR = 1.24), both of which meet genome-wide significance. Both of these loci were overlooked in the initial replication, despite being among the top 3000 (∼1%) SNP hits in the original screen. Oxford University Press 2010-03-01 2009-12-09 /pmc/articles/PMC2816610/ /pubmed/20007504 http://dx.doi.org/10.1093/hmg/ddp542 Text en © The Author 2009. Published by Oxford University Press. http://creativecommons.org/licenses/by-nc/2.0/uk/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Association Studies Articles McCauley, Jacob L. Zuvich, Rebecca L. Beecham, Ashley H. De Jager, Philip L. Konidari, Ioanna Whitehead, Patrice L. Aubin, Cristin Ban, Maria Pobywajlo, Susan Briskin, Rebeccah Romano, Susan Aggarwal, Neelum T. Piccio, Laura McArdle, Wendy L. Strachan, David P. Evans, Denis Cross, Anne H. Cree, Bruce Rioux, John D. Barcellos, Lisa F. Ivinson, Adrian J. Compston, Alastair Hafler, David A. Hauser, Stephen L. Oksenberg, Jorge R. Sawcer, Stephen J. Pericak-Vance, Margaret A. Haines, Jonathan L. Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci |
title | Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci |
title_full | Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci |
title_fullStr | Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci |
title_full_unstemmed | Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci |
title_short | Comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies KIF21B and TMEM39A as susceptibility loci |
title_sort | comprehensive follow-up of the first genome-wide association study of multiple sclerosis identifies kif21b and tmem39a as susceptibility loci |
topic | Association Studies Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2816610/ https://www.ncbi.nlm.nih.gov/pubmed/20007504 http://dx.doi.org/10.1093/hmg/ddp542 |
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