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rs2072135, a low‐penetrance variant for chronic lymphocytic leukaemia?
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Titel: |
rs2072135, a low‐penetrance variant for chronic lymphocytic leukaemia? |
In: | British Journal of Haematology, 162, 2013, 2, S. 221-228 |
veröffentlicht: |
Wiley
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Umfang: | 221-228 |
ISSN: |
1365-2141 0007-1048 |
DOI: | 10.1111/bjh.12366 |
Zusammenfassung: | <jats:title>Summary</jats:title><jats:p>Recent multi‐stage genome‐wide association studies (<jats:styled-content style="fixed-case">GWAS</jats:styled-content>) have identified single nucleotide polymorphisms (<jats:styled-content style="fixed-case">SNP</jats:styled-content>s) that are robustly associated with chronic lymphocytic leukaemia (<jats:styled-content style="fixed-case">CLL</jats:styled-content>) risk. Given that most of these <jats:styled-content style="fixed-case">SNP</jats:styled-content>s map to non‐coding regions of the genome, it suggests that the functional basis of many <jats:styled-content style="fixed-case">GWAS</jats:styled-content> signals will be through differential gene expression. By referencing publically accessible expression quantitative trait loci (<jats:styled-content style="fixed-case">eQTL</jats:styled-content>) data on lymphoblastoid cells lines (<jats:styled-content style="fixed-case">LCLs</jats:styled-content>) we have globally demonstrated an association between <jats:styled-content style="fixed-case">GWAS </jats:styled-content><jats:italic>P</jats:italic>‐values and <jats:styled-content style="fixed-case">eQTL</jats:styled-content>s, consistent with much of the variation in <jats:styled-content style="fixed-case">CLL</jats:styled-content> risk being defined by variants impacting on gene expression. To explore using <jats:styled-content style="fixed-case">eQTL</jats:styled-content> data to select <jats:styled-content style="fixed-case">GWAS SNP</jats:styled-content>s for replication, we genotyped rs2072135 (<jats:styled-content style="fixed-case">GWAS </jats:styled-content><jats:italic>P</jats:italic>‐value = 0·0024, <jats:styled-content style="fixed-case">eQTL </jats:styled-content><jats:italic>P</jats:italic>‐value = 1·510<jats:sup>−19</jats:sup>) in five independent case‐control series totalling 1968 cases and 3538 controls. While not attaining statistical significance (combined <jats:italic>P</jats:italic>‐value = 1 × 10<jats:sup>−4</jats:sup>), rs2072135 defines a promising risk locus for <jats:styled-content style="fixed-case">CLL</jats:styled-content>. Incorporating <jats:styled-content style="fixed-case">eQTL</jats:styled-content> information offers an attractive strategy for selecting <jats:styled-content style="fixed-case">SNP</jats:styled-content>s from <jats:styled-content style="fixed-case">GWAS</jats:styled-content> for validation.</jats:p> |
Format: | E-Article |
Quelle: | Wiley (CrossRef) |
Sprache: | Englisch |