Improving the estimation of celiac disease sibling risk by non-HLA genes.
Celiac Disease (CD) is a polygenic trait, and HLA genes explain less than half of the genetic variation. Through large GWAs more than 40 associated non-HLA genes were identified, but they give a small contribution to the heritability of the disease. The aim of this study is to improve the estimate o...
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doaj-750219d99cf54a0c9f4f21c8937e6e8f2020-11-25T02:31:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-01611e2692010.1371/journal.pone.0026920Improving the estimation of celiac disease sibling risk by non-HLA genes.Valentina IzzoMichele PinelliNadia TintoMaria Valeria EspositoArturo ColaMaria Pia SperandeoFrancesca TucciSergio CocozzaLuigi GrecoLucia SacchettiCeliac Disease (CD) is a polygenic trait, and HLA genes explain less than half of the genetic variation. Through large GWAs more than 40 associated non-HLA genes were identified, but they give a small contribution to the heritability of the disease. The aim of this study is to improve the estimate of the CD risk in siblings, by adding to HLA a small set of non-HLA genes. One-hundred fifty-seven Italian families with a confirmed CD case and at least one other sib and both parents were recruited. Among 249 sibs, 29 developed CD in a 6 year follow-up period. All individuals were typed for HLA and 10 SNPs in non-HLA genes: CCR1/CCR3 (rs6441961), IL12A/SCHIP1 and IL12A (rs17810546 and rs9811792), TAGAP (rs1738074), RGS1 (rs2816316), LPP (rs1464510), OLIG3 (rs2327832), REL (rs842647), IL2/IL21 (rs6822844), SH2B3 (rs3184504). Three associated SNPs (in LPP, REL, and RGS1 genes) were identified through the Transmission Disequilibrium Test and a Bayesian approach was used to assign a score (BS) to each detected HLA+SNPs genotype combination. We then classified CD sibs as at low or at high risk if their BS was respectively < or ≥ median BS value within each HLA risk group. A larger number (72%) of CD sibs showed a BS ≥ the median value and had a more than two fold higher OR than CD sibs with a BS value < the median (O.R = 2.53, p = 0.047). Our HLA+SNPs genotype classification, showed both a higher predictive negative value (95% vs 91%) and diagnostic sensitivity (79% vs 45%) than the HLA only. In conclusion, the estimate of the CD risk by HLA+SNPs approach, even if not applicable to prevention, could be a precious tool to improve the prediction of the disease in a cohort of first degree relatives, particularly in the low HLA risk groups.http://europepmc.org/articles/PMC3210127?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Valentina Izzo Michele Pinelli Nadia Tinto Maria Valeria Esposito Arturo Cola Maria Pia Sperandeo Francesca Tucci Sergio Cocozza Luigi Greco Lucia Sacchetti |
spellingShingle |
Valentina Izzo Michele Pinelli Nadia Tinto Maria Valeria Esposito Arturo Cola Maria Pia Sperandeo Francesca Tucci Sergio Cocozza Luigi Greco Lucia Sacchetti Improving the estimation of celiac disease sibling risk by non-HLA genes. PLoS ONE |
author_facet |
Valentina Izzo Michele Pinelli Nadia Tinto Maria Valeria Esposito Arturo Cola Maria Pia Sperandeo Francesca Tucci Sergio Cocozza Luigi Greco Lucia Sacchetti |
author_sort |
Valentina Izzo |
title |
Improving the estimation of celiac disease sibling risk by non-HLA genes. |
title_short |
Improving the estimation of celiac disease sibling risk by non-HLA genes. |
title_full |
Improving the estimation of celiac disease sibling risk by non-HLA genes. |
title_fullStr |
Improving the estimation of celiac disease sibling risk by non-HLA genes. |
title_full_unstemmed |
Improving the estimation of celiac disease sibling risk by non-HLA genes. |
title_sort |
improving the estimation of celiac disease sibling risk by non-hla genes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Celiac Disease (CD) is a polygenic trait, and HLA genes explain less than half of the genetic variation. Through large GWAs more than 40 associated non-HLA genes were identified, but they give a small contribution to the heritability of the disease. The aim of this study is to improve the estimate of the CD risk in siblings, by adding to HLA a small set of non-HLA genes. One-hundred fifty-seven Italian families with a confirmed CD case and at least one other sib and both parents were recruited. Among 249 sibs, 29 developed CD in a 6 year follow-up period. All individuals were typed for HLA and 10 SNPs in non-HLA genes: CCR1/CCR3 (rs6441961), IL12A/SCHIP1 and IL12A (rs17810546 and rs9811792), TAGAP (rs1738074), RGS1 (rs2816316), LPP (rs1464510), OLIG3 (rs2327832), REL (rs842647), IL2/IL21 (rs6822844), SH2B3 (rs3184504). Three associated SNPs (in LPP, REL, and RGS1 genes) were identified through the Transmission Disequilibrium Test and a Bayesian approach was used to assign a score (BS) to each detected HLA+SNPs genotype combination. We then classified CD sibs as at low or at high risk if their BS was respectively < or ≥ median BS value within each HLA risk group. A larger number (72%) of CD sibs showed a BS ≥ the median value and had a more than two fold higher OR than CD sibs with a BS value < the median (O.R = 2.53, p = 0.047). Our HLA+SNPs genotype classification, showed both a higher predictive negative value (95% vs 91%) and diagnostic sensitivity (79% vs 45%) than the HLA only. In conclusion, the estimate of the CD risk by HLA+SNPs approach, even if not applicable to prevention, could be a precious tool to improve the prediction of the disease in a cohort of first degree relatives, particularly in the low HLA risk groups. |
url |
http://europepmc.org/articles/PMC3210127?pdf=render |
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