Genomic prediction of celiac disease targeting HLA-positive individuals
Identifieur interne : 000B79 ( Pmc/Curation ); précédent : 000B78; suivant : 000B80Genomic prediction of celiac disease targeting HLA-positive individuals
Auteurs : Gad Abraham [Australie] ; Alexia Rohmer [Australie] ; Jason A. Tye-Din [Australie] ; Michael Inouye [Australie]Source :
- Genome Medicine [ 1756-994X ] ; 2015.
Abstract
Genomic prediction aims to leverage genome-wide genetic data towards better disease diagnostics and risk scores. We have previously published a genomic risk score (GRS) for celiac disease (CD), a common and highly heritable autoimmune disease, which differentiates between CD cases and population-based controls at a clinically-relevant predictive level, improving upon other gene-based approaches. HLA risk haplotypes, particularly HLA-DQ2.5, are necessary but not sufficient for CD, with at least one HLA risk haplotype present in up to half of most Caucasian populations. Here, we assess a genomic prediction strategy that specifically targets this common genetic susceptibility subtype, utilizing a supervised learning procedure for CD that leverages known HLA-DQ2.5 risk.
Using L1/L2-regularized support-vector machines trained on large European case-control datasets, we constructed novel CD GRSs specific to individuals with HLA-DQ2.5 risk haplotypes (GRS-DQ2.5) and compared them with the predictive power of the existing CD GRS (GRS14) as well as two haplotype-based approaches, externally validating the results in a North American case-control study.
Consistent with previous observations, both the existing GRS14 and the GRS-DQ2.5 had better predictive performance than the HLA haplotype approaches. GRS-DQ2.5 models, based on directly genotyped or imputed markers, achieved similar levels of predictive performance (AUC = 0.718-0.73), which were substantially higher than those obtained from the DQ2.5 zygosity alone (AUC = 0.558), the HLA risk haplotype method (AUC = 0.634), or the generic GRS14 (AUC = 0.679). In a screening model of at-risk individuals, the GRS-DQ2.5 lowered the number of unnecessary follow-up tests for CD across most sensitivity levels. Relative to a baseline implicating all DQ2.5-positive individuals for follow-up, the GRS-DQ2.5 resulted in a net saving of 2.2 unnecessary follow-up tests for each justified test while still capturing 90 % of DQ2.5-positive CD cases.
Genomic risk scores for CD that target genetically at-risk sub-groups improve predictive performance beyond traditional approaches and may represent a useful strategy for prioritizing individuals at increased risk of disease, thus potentially reducing unnecessary follow-up diagnostic tests.
The online version of this article (doi:10.1186/s13073-015-0196-5) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s13073-015-0196-5
PubMed: 26244058
PubMed Central: 4523954
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Alexia Rohmer<affiliation><nlm:aff id="Aff3">Faculty of Life Science, University of Strasbourg, Strasbourg, 67084 CEDEX France</nlm:aff>
<wicri:noCountry code="subfield">67084 CEDEX France</wicri:noCountry>
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<affiliation><nlm:aff id="Aff4">The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052 Victoria Australia</nlm:aff>
<wicri:noCountry code="subfield">3052 Victoria Australia</wicri:noCountry>
</affiliation>
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<affiliation><nlm:aff id="Aff6">Department of Gastroenterology, The Royal Melbourne Hospital, Grattan St., Parkville, 3050 Victoria Australia</nlm:aff>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>Genomic prediction aims to leverage genome-wide genetic data towards better disease diagnostics and risk scores. We have previously published a genomic risk score (GRS) for celiac disease (CD), a common and highly heritable autoimmune disease, which differentiates between CD cases and population-based controls at a clinically-relevant predictive level, improving upon other gene-based approaches. HLA risk haplotypes, particularly HLA-DQ2.5, are necessary but not sufficient for CD, with at least one HLA risk haplotype present in up to half of most Caucasian populations. Here, we assess a genomic prediction strategy that specifically targets this common genetic susceptibility subtype, utilizing a supervised learning procedure for CD that leverages known HLA-DQ2.5 risk.</p>
</sec>
<sec><title>Methods</title>
<p>Using L1/L2-regularized support-vector machines trained on large European case-control datasets, we constructed novel CD GRSs specific to individuals with HLA-DQ2.5 risk haplotypes (GRS-DQ2.5) and compared them with the predictive power of the existing CD GRS (GRS14) as well as two haplotype-based approaches, externally validating the results in a North American case-control study.</p>
</sec>
<sec><title>Results</title>
<p>Consistent with previous observations, both the existing GRS14 and the GRS-DQ2.5 had better predictive performance than the HLA haplotype approaches. GRS-DQ2.5 models, based on directly genotyped or imputed markers, achieved similar levels of predictive performance (AUC = 0.718-0.73), which were substantially higher than those obtained from the DQ2.5 zygosity alone (AUC = 0.558), the HLA risk haplotype method (AUC = 0.634), or the generic GRS14 (AUC = 0.679). In a screening model of at-risk individuals, the GRS-DQ2.5 lowered the number of unnecessary follow-up tests for CD across most sensitivity levels. Relative to a baseline implicating all DQ2.5-positive individuals for follow-up, the GRS-DQ2.5 resulted in a net saving of 2.2 unnecessary follow-up tests for each justified test while still capturing 90 % of DQ2.5-positive CD cases.</p>
</sec>
<sec><title>Conclusions</title>
<p>Genomic risk scores for CD that target genetically at-risk sub-groups improve predictive performance beyond traditional approaches and may represent a useful strategy for prioritizing individuals at increased risk of disease, thus potentially reducing unnecessary follow-up diagnostic tests.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s13073-015-0196-5) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
<back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Graham, Rr" uniqKey="Graham R">RR Graham</name>
</author>
<author><name sortKey="Cotsapas, C" uniqKey="Cotsapas C">C Cotsapas</name>
</author>
<author><name sortKey="Davies, L" uniqKey="Davies L">L Davies</name>
</author>
<author><name sortKey="Hackett, R" uniqKey="Hackett R">R Hackett</name>
</author>
<author><name sortKey="Lessard, Cj" uniqKey="Lessard C">CJ Lessard</name>
</author>
<author><name sortKey="Leon, Jm" uniqKey="Leon J">JM Leon</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ramos, Ps" uniqKey="Ramos P">PS Ramos</name>
</author>
<author><name sortKey="Criswell, La" uniqKey="Criswell L">LA Criswell</name>
</author>
<author><name sortKey="Moser, Kl" uniqKey="Moser K">KL Moser</name>
</author>
<author><name sortKey="Comeau, Me" uniqKey="Comeau M">ME Comeau</name>
</author>
<author><name sortKey="Williams, Ah" uniqKey="Williams A">AH Williams</name>
</author>
<author><name sortKey="Pajewski, Nm" uniqKey="Pajewski N">NM Pajewski</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Trynka, G" uniqKey="Trynka G">G Trynka</name>
</author>
<author><name sortKey="Hunt, K" uniqKey="Hunt K">K Hunt</name>
</author>
<author><name sortKey="Bockett, N" uniqKey="Bockett N">N Bockett</name>
</author>
<author><name sortKey="Romanos, J" uniqKey="Romanos J">J Romanos</name>
</author>
<author><name sortKey="Mistry, V" uniqKey="Mistry V">V Mistry</name>
</author>
<author><name sortKey="Szperl, A" uniqKey="Szperl A">A Szperl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Dubois, Pca" uniqKey="Dubois P">PCA Dubois</name>
</author>
<author><name sortKey="Trynka, G" uniqKey="Trynka G">G Trynka</name>
</author>
<author><name sortKey="Franke, L" uniqKey="Franke L">L Franke</name>
</author>
<author><name sortKey="Hunt, K" uniqKey="Hunt K">K Hunt</name>
</author>
<author><name sortKey="Romanos, J" uniqKey="Romanos J">J Romanos</name>
</author>
<author><name sortKey="Curtotti, A" uniqKey="Curtotti A">A Curtotti</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Barrett, Jc" uniqKey="Barrett J">JC Barrett</name>
</author>
<author><name sortKey="Clayton, Dg" uniqKey="Clayton D">DG Clayton</name>
</author>
<author><name sortKey="Concannon, P" uniqKey="Concannon P">P Concannon</name>
</author>
<author><name sortKey="Akolkar, B" uniqKey="Akolkar B">B Akolkar</name>
</author>
<author><name sortKey="Cooper, Jd" uniqKey="Cooper J">JD Cooper</name>
</author>
<author><name sortKey="Erlich, Ha" uniqKey="Erlich H">HA Erlich</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zhernakova, A" uniqKey="Zhernakova A">A Zhernakova</name>
</author>
<author><name sortKey="Stahl, Ea" uniqKey="Stahl E">EA Stahl</name>
</author>
<author><name sortKey="Trynka, G" uniqKey="Trynka G">G Trynka</name>
</author>
<author><name sortKey="Raychaudhuri, S" uniqKey="Raychaudhuri S">S Raychaudhuri</name>
</author>
<author><name sortKey="Festen, Ea" uniqKey="Festen E">EA Festen</name>
</author>
<author><name sortKey="Franke, L" uniqKey="Franke L">L Franke</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wei, Z" uniqKey="Wei Z">Z Wei</name>
</author>
<author><name sortKey="Wang, K" uniqKey="Wang K">K Wang</name>
</author>
<author><name sortKey="Qu, Hq" uniqKey="Qu H">HQ Qu</name>
</author>
<author><name sortKey="Zhang, H" uniqKey="Zhang H">H Zhang</name>
</author>
<author><name sortKey="Bradfield, J" uniqKey="Bradfield J">J Bradfield</name>
</author>
<author><name sortKey="Kim, C" uniqKey="Kim C">C Kim</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abraham, G" uniqKey="Abraham G">G Abraham</name>
</author>
<author><name sortKey="Tye Din, Ja" uniqKey="Tye Din J">JA Tye-Din</name>
</author>
<author><name sortKey="Bhalala, Og" uniqKey="Bhalala O">OG Bhalala</name>
</author>
<author><name sortKey="Kowalczyk, A" uniqKey="Kowalczyk A">A Kowalczyk</name>
</author>
<author><name sortKey="Zobel, J" uniqKey="Zobel J">J Zobel</name>
</author>
<author><name sortKey="Inouye, M" uniqKey="Inouye M">M Inouye</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wei, Z" uniqKey="Wei Z">Z Wei</name>
</author>
<author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name>
</author>
<author><name sortKey="Bradfield, J" uniqKey="Bradfield J">J Bradfield</name>
</author>
<author><name sortKey="Li, J" uniqKey="Li J">J Li</name>
</author>
<author><name sortKey="Cardinale, C" uniqKey="Cardinale C">C Cardinale</name>
</author>
<author><name sortKey="Frackelton, E" uniqKey="Frackelton E">E Frackelton</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hoggart, Cj" uniqKey="Hoggart C">CJ Hoggart</name>
</author>
<author><name sortKey="Whittaker, Jc" uniqKey="Whittaker J">JC Whittaker</name>
</author>
<author><name sortKey="De Iorio, M" uniqKey="De Iorio M">M De Iorio</name>
</author>
<author><name sortKey="Balding, Dj" uniqKey="Balding D">DJ Balding</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Speed, D" uniqKey="Speed D">D Speed</name>
</author>
<author><name sortKey="Balding, Dj" uniqKey="Balding D">DJ Balding</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abraham, G" uniqKey="Abraham G">G Abraham</name>
</author>
<author><name sortKey="Kowalczyk, A" uniqKey="Kowalczyk A">A Kowalczyk</name>
</author>
<author><name sortKey="Zobel, J" uniqKey="Zobel J">J Zobel</name>
</author>
<author><name sortKey="Inouye, M" uniqKey="Inouye M">M Inouye</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Husby, S" uniqKey="Husby S">S Husby</name>
</author>
<author><name sortKey="Koletzko, S" uniqKey="Koletzko S">S Koletzko</name>
</author>
<author><name sortKey="Korponay Szabo, Ir" uniqKey="Korponay Szabo I">IR Korponay-Szabo</name>
</author>
<author><name sortKey="Mearin, Ml" uniqKey="Mearin M">ML Mearin</name>
</author>
<author><name sortKey="Phillips, A" uniqKey="Phillips A">A Phillips</name>
</author>
<author><name sortKey="Shamir, R" uniqKey="Shamir R">R Shamir</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abadie, V" uniqKey="Abadie V">V Abadie</name>
</author>
<author><name sortKey="Sollid, Lm" uniqKey="Sollid L">LM Sollid</name>
</author>
<author><name sortKey="Barreiro, Lb" uniqKey="Barreiro L">LB Barreiro</name>
</author>
<author><name sortKey="Jabri, B" uniqKey="Jabri B">B Jabri</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Heel, D" uniqKey="Van Heel D">D van Heel</name>
</author>
<author><name sortKey="West, J" uniqKey="West J">J West</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Nistico, L" uniqKey="Nistico L">L Nistico</name>
</author>
<author><name sortKey="Fagnani, C" uniqKey="Fagnani C">C Fagnani</name>
</author>
<author><name sortKey="Coto, I" uniqKey="Coto I">I Coto</name>
</author>
<author><name sortKey="Percopo, S" uniqKey="Percopo S">S Percopo</name>
</author>
<author><name sortKey="Cotichini, R" uniqKey="Cotichini R">R Cotichini</name>
</author>
<author><name sortKey="Limongelli, Mg" uniqKey="Limongelli M">MG Limongelli</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Karell, K" uniqKey="Karell K">K Karell</name>
</author>
<author><name sortKey="Louka, As" uniqKey="Louka A">AS Louka</name>
</author>
<author><name sortKey="Moodie, Sj" uniqKey="Moodie S">SJ Moodie</name>
</author>
<author><name sortKey="Ascher, H" uniqKey="Ascher H">H Ascher</name>
</author>
<author><name sortKey="Clot, F" uniqKey="Clot F">F Clot</name>
</author>
<author><name sortKey="Greco, L" uniqKey="Greco L">L Greco</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tye Din, Ja" uniqKey="Tye Din J">JA Tye-Din</name>
</author>
<author><name sortKey="Stewart, Ja" uniqKey="Stewart J">JA Stewart</name>
</author>
<author><name sortKey="Dromey, Ja" uniqKey="Dromey J">JA Dromey</name>
</author>
<author><name sortKey="Beissbarth, T" uniqKey="Beissbarth T">T Beissbarth</name>
</author>
<author><name sortKey="Van Heel, Da" uniqKey="Van Heel D">DA van Heel</name>
</author>
<author><name sortKey="Tatham, A" uniqKey="Tatham A">A Tatham</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Hunt, Ka" uniqKey="Hunt K">KA Hunt</name>
</author>
<author><name sortKey="Zhernakova, A" uniqKey="Zhernakova A">A Zhernakova</name>
</author>
<author><name sortKey="Turner, G" uniqKey="Turner G">G Turner</name>
</author>
<author><name sortKey="Heap, Ga" uniqKey="Heap G">GA Heap</name>
</author>
<author><name sortKey="Franke, L" uniqKey="Franke L">L Franke</name>
</author>
<author><name sortKey="Bruinenberg, M" uniqKey="Bruinenberg M">M Bruinenberg</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Ahn, R" uniqKey="Ahn R">R Ahn</name>
</author>
<author><name sortKey="Ding, Yc" uniqKey="Ding Y">YC Ding</name>
</author>
<author><name sortKey="Murray, J" uniqKey="Murray J">J Murray</name>
</author>
<author><name sortKey="Fasano, A" uniqKey="Fasano A">A Fasano</name>
</author>
<author><name sortKey="Green, Ph" uniqKey="Green P">PH Green</name>
</author>
<author><name sortKey="Neuhausen, Sl" uniqKey="Neuhausen S">SL Neuhausen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Festen, Ea" uniqKey="Festen E">EA Festen</name>
</author>
<author><name sortKey="Goyette, P" uniqKey="Goyette P">P Goyette</name>
</author>
<author><name sortKey="Green, T" uniqKey="Green T">T Green</name>
</author>
<author><name sortKey="Boucher, G" uniqKey="Boucher G">G Boucher</name>
</author>
<author><name sortKey="Beauchamp, C" uniqKey="Beauchamp C">C Beauchamp</name>
</author>
<author><name sortKey="Trynka, G" uniqKey="Trynka G">G Trynka</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Garner, C" uniqKey="Garner C">C Garner</name>
</author>
<author><name sortKey="Ahn, R" uniqKey="Ahn R">R Ahn</name>
</author>
<author><name sortKey="Ding, Yc" uniqKey="Ding Y">YC Ding</name>
</author>
<author><name sortKey="Steele, L" uniqKey="Steele L">L Steele</name>
</author>
<author><name sortKey="Stoven, S" uniqKey="Stoven S">S Stoven</name>
</author>
<author><name sortKey="Green, Ph" uniqKey="Green P">PH Green</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Tye Din, Ja" uniqKey="Tye Din J">JA Tye-Din</name>
</author>
<author><name sortKey="Cameron, Dj" uniqKey="Cameron D">DJ Cameron</name>
</author>
<author><name sortKey="Daveson, Aj" uniqKey="Daveson A">AJ Daveson</name>
</author>
<author><name sortKey="Day, As" uniqKey="Day A">AS Day</name>
</author>
<author><name sortKey="Dellsperger, P" uniqKey="Dellsperger P">P Dellsperger</name>
</author>
<author><name sortKey="Hogan, C" uniqKey="Hogan C">C Hogan</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Anderson, Rp" uniqKey="Anderson R">RP Anderson</name>
</author>
<author><name sortKey="Henry, Mj" uniqKey="Henry M">MJ Henry</name>
</author>
<author><name sortKey="Taylor, R" uniqKey="Taylor R">R Taylor</name>
</author>
<author><name sortKey="Duncan, El" uniqKey="Duncan E">EL Duncan</name>
</author>
<author><name sortKey="Danoy, P" uniqKey="Danoy P">P Danoy</name>
</author>
<author><name sortKey="Costa, Mj" uniqKey="Costa M">MJ Costa</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Lionetti, E" uniqKey="Lionetti E">E Lionetti</name>
</author>
<author><name sortKey="Castellaneta, S" uniqKey="Castellaneta S">S Castellaneta</name>
</author>
<author><name sortKey="Francavilla, R" uniqKey="Francavilla R">R Francavilla</name>
</author>
<author><name sortKey="Pulvirenti, A" uniqKey="Pulvirenti A">A Pulvirenti</name>
</author>
<author><name sortKey="Tonutti, E" uniqKey="Tonutti E">E Tonutti</name>
</author>
<author><name sortKey="Amarri, S" uniqKey="Amarri S">S Amarri</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Liu, E" uniqKey="Liu E">E Liu</name>
</author>
<author><name sortKey="Lee, Hs" uniqKey="Lee H">HS Lee</name>
</author>
<author><name sortKey="Aronsson, Ca" uniqKey="Aronsson C">CA Aronsson</name>
</author>
<author><name sortKey="Hagopian, Wa" uniqKey="Hagopian W">WA Hagopian</name>
</author>
<author><name sortKey="Koletzko, S" uniqKey="Koletzko S">S Koletzko</name>
</author>
<author><name sortKey="Rewers, Mj" uniqKey="Rewers M">MJ Rewers</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Karinen, H" uniqKey="Karinen H">H Karinen</name>
</author>
<author><name sortKey="Karkkainen, P" uniqKey="Karkkainen P">P Karkkainen</name>
</author>
<author><name sortKey="Pihlajamaki, J" uniqKey="Pihlajamaki J">J Pihlajamaki</name>
</author>
<author><name sortKey="Janatuinen, E" uniqKey="Janatuinen E">E Janatuinen</name>
</author>
<author><name sortKey="Heikkinen, M" uniqKey="Heikkinen M">M Heikkinen</name>
</author>
<author><name sortKey="Julkunen, R" uniqKey="Julkunen R">R Julkunen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Al Toma, A" uniqKey="Al Toma A">A Al-Toma</name>
</author>
<author><name sortKey="Goerres, Ms" uniqKey="Goerres M">MS Goerres</name>
</author>
<author><name sortKey="Meijer, Jw" uniqKey="Meijer J">JW Meijer</name>
</author>
<author><name sortKey="Pena, As" uniqKey="Pena A">AS Pena</name>
</author>
<author><name sortKey="Crusius, Jb" uniqKey="Crusius J">JB Crusius</name>
</author>
<author><name sortKey="Mulder, Cj" uniqKey="Mulder C">CJ Mulder</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Biagi, F" uniqKey="Biagi F">F Biagi</name>
</author>
<author><name sortKey="Schiepatti, A" uniqKey="Schiepatti A">A Schiepatti</name>
</author>
<author><name sortKey="Malamut, G" uniqKey="Malamut G">G Malamut</name>
</author>
<author><name sortKey="Marchese, A" uniqKey="Marchese A">A Marchese</name>
</author>
<author><name sortKey="Cellier, C" uniqKey="Cellier C">C Cellier</name>
</author>
<author><name sortKey="Bakker, Sf" uniqKey="Bakker S">SF Bakker</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abraham, G" uniqKey="Abraham G">G Abraham</name>
</author>
<author><name sortKey="Kowalczyk, A" uniqKey="Kowalczyk A">A Kowalczyk</name>
</author>
<author><name sortKey="Zobel, J" uniqKey="Zobel J">J Zobel</name>
</author>
<author><name sortKey="Inouye, M" uniqKey="Inouye M">M Inouye</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Okser, S" uniqKey="Okser S">S Okser</name>
</author>
<author><name sortKey="Pahikkala, T" uniqKey="Pahikkala T">T Pahikkala</name>
</author>
<author><name sortKey="Airola, A" uniqKey="Airola A">A Airola</name>
</author>
<author><name sortKey="Salakoski, T" uniqKey="Salakoski T">T Salakoski</name>
</author>
<author><name sortKey="Ripatti, S" uniqKey="Ripatti S">S Ripatti</name>
</author>
<author><name sortKey="Aittokallio, T" uniqKey="Aittokallio T">T Aittokallio</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Van Heel, Da" uniqKey="Van Heel D">DA van Heel</name>
</author>
<author><name sortKey="Franke, L" uniqKey="Franke L">L Franke</name>
</author>
<author><name sortKey="Hunt, Ka" uniqKey="Hunt K">KA Hunt</name>
</author>
<author><name sortKey="Gwilliam, R" uniqKey="Gwilliam R">R Gwilliam</name>
</author>
<author><name sortKey="Zhernakova, A" uniqKey="Zhernakova A">A Zhernakova</name>
</author>
<author><name sortKey="Inouye, M" uniqKey="Inouye M">M Inouye</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Romanos, J" uniqKey="Romanos J">J Romanos</name>
</author>
<author><name sortKey="Rosen, A" uniqKey="Rosen A">A Rosen</name>
</author>
<author><name sortKey="Kumar, V" uniqKey="Kumar V">V Kumar</name>
</author>
<author><name sortKey="Trynka, G" uniqKey="Trynka G">G Trynka</name>
</author>
<author><name sortKey="Franke, L" uniqKey="Franke L">L Franke</name>
</author>
<author><name sortKey="Szperl, A" uniqKey="Szperl A">A Szperl</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Gutierrez Achury, J" uniqKey="Gutierrez Achury J">J Gutierrez-Achury</name>
</author>
<author><name sortKey="Zhernakova, A" uniqKey="Zhernakova A">A Zhernakova</name>
</author>
<author><name sortKey="Pulit, Sl" uniqKey="Pulit S">SL Pulit</name>
</author>
<author><name sortKey="Trynka, G" uniqKey="Trynka G">G Trynka</name>
</author>
<author><name sortKey="Hunt, Ka" uniqKey="Hunt K">KA Hunt</name>
</author>
<author><name sortKey="Romanos, J" uniqKey="Romanos J">J Romanos</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Jia, X" uniqKey="Jia X">X Jia</name>
</author>
<author><name sortKey="Han, B" uniqKey="Han B">B Han</name>
</author>
<author><name sortKey="Onengut Gumuscu, S" uniqKey="Onengut Gumuscu S">S Onengut-Gumuscu</name>
</author>
<author><name sortKey="Chen, Wm" uniqKey="Chen W">WM Chen</name>
</author>
<author><name sortKey="Concannon, Pj" uniqKey="Concannon P">PJ Concannon</name>
</author>
<author><name sortKey="Rich, Ss" uniqKey="Rich S">SS Rich</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Garner, Cp" uniqKey="Garner C">CP Garner</name>
</author>
<author><name sortKey="Murray, Ja" uniqKey="Murray J">JA Murray</name>
</author>
<author><name sortKey="Ding, Yc" uniqKey="Ding Y">YC Ding</name>
</author>
<author><name sortKey="Tien, Z" uniqKey="Tien Z">Z Tien</name>
</author>
<author><name sortKey="Van Heel, Da" uniqKey="Van Heel D">DA van Heel</name>
</author>
<author><name sortKey="Neuhausen, Sl" uniqKey="Neuhausen S">SL Neuhausen</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Wray, Nr" uniqKey="Wray N">NR Wray</name>
</author>
<author><name sortKey="Yang, J" uniqKey="Yang J">J Yang</name>
</author>
<author><name sortKey="Hayes, Bj" uniqKey="Hayes B">BJ Hayes</name>
</author>
<author><name sortKey="Price, Al" uniqKey="Price A">AL Price</name>
</author>
<author><name sortKey="Goddard, Me" uniqKey="Goddard M">ME Goddard</name>
</author>
<author><name sortKey="Visscher, Pm" uniqKey="Visscher P">PM Visscher</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Purcell, S" uniqKey="Purcell S">S Purcell</name>
</author>
<author><name sortKey="Neale, B" uniqKey="Neale B">B Neale</name>
</author>
<author><name sortKey="Todd Brown, K" uniqKey="Todd Brown K">K Todd-Brown</name>
</author>
<author><name sortKey="Thomas, L" uniqKey="Thomas L">L Thomas</name>
</author>
<author><name sortKey="Ferreira, Ma" uniqKey="Ferreira M">MA Ferreira</name>
</author>
<author><name sortKey="Bender, D" uniqKey="Bender D">D Bender</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Chang, Cc" uniqKey="Chang C">CC Chang</name>
</author>
<author><name sortKey="Chow, Cc" uniqKey="Chow C">CC Chow</name>
</author>
<author><name sortKey="Tellier, Lc" uniqKey="Tellier L">LC Tellier</name>
</author>
<author><name sortKey="Vattikuti, S" uniqKey="Vattikuti S">S Vattikuti</name>
</author>
<author><name sortKey="Purcell, Sm" uniqKey="Purcell S">SM Purcell</name>
</author>
<author><name sortKey="Lee, Jj" uniqKey="Lee J">JJ Lee</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Abraham, G" uniqKey="Abraham G">G Abraham</name>
</author>
<author><name sortKey="Inouye, M" uniqKey="Inouye M">M Inouye</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Weir, Bs" uniqKey="Weir B">BS Weir</name>
</author>
<author><name sortKey="Cockerham, Cc" uniqKey="Cockerham C">CC Cockerham</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Zheng, X" uniqKey="Zheng X">X Zheng</name>
</author>
<author><name sortKey="Shen, J" uniqKey="Shen J">J Shen</name>
</author>
<author><name sortKey="Cox, C" uniqKey="Cox C">C Cox</name>
</author>
<author><name sortKey="Wakefield, Jc" uniqKey="Wakefield J">JC Wakefield</name>
</author>
<author><name sortKey="Ehm, Mg" uniqKey="Ehm M">MG Ehm</name>
</author>
<author><name sortKey="Nelson, Mr" uniqKey="Nelson M">MR Nelson</name>
</author>
</analytic>
</biblStruct>
<biblStruct></biblStruct>
<biblStruct><analytic><author><name sortKey="Harrell, Fej" uniqKey="Harrell F">FEJ Harrell</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Robin, X" uniqKey="Robin X">X Robin</name>
</author>
<author><name sortKey="Turck, N" uniqKey="Turck N">N Turck</name>
</author>
<author><name sortKey="Hainard, A" uniqKey="Hainard A">A Hainard</name>
</author>
<author><name sortKey="Tiberti, N" uniqKey="Tiberti N">N Tiberti</name>
</author>
<author><name sortKey="Lisacek, F" uniqKey="Lisacek F">F Lisacek</name>
</author>
<author><name sortKey="Sanchez, Jc" uniqKey="Sanchez J">JC Sanchez</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Megiorni, F" uniqKey="Megiorni F">F Megiorni</name>
</author>
<author><name sortKey="Mora, B" uniqKey="Mora B">B Mora</name>
</author>
<author><name sortKey="Bonamico, M" uniqKey="Bonamico M">M Bonamico</name>
</author>
<author><name sortKey="Barbato, M" uniqKey="Barbato M">M Barbato</name>
</author>
<author><name sortKey="Nenna, R" uniqKey="Nenna R">R Nenna</name>
</author>
<author><name sortKey="Maiella, G" uniqKey="Maiella G">G Maiella</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Fasano, A" uniqKey="Fasano A">A Fasano</name>
</author>
<author><name sortKey="Berti, I" uniqKey="Berti I">I Berti</name>
</author>
<author><name sortKey="Gerarduzzi, T" uniqKey="Gerarduzzi T">T Gerarduzzi</name>
</author>
<author><name sortKey="Not, T" uniqKey="Not T">T Not</name>
</author>
<author><name sortKey="Colletti, Rb" uniqKey="Colletti R">RB Colletti</name>
</author>
<author><name sortKey="Drago, S" uniqKey="Drago S">S Drago</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Husby, S" uniqKey="Husby S">S Husby</name>
</author>
<author><name sortKey="Murray, Ja" uniqKey="Murray J">JA Murray</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Sollid, Lm" uniqKey="Sollid L">LM Sollid</name>
</author>
<author><name sortKey="Lie, Ba" uniqKey="Lie B">BA Lie</name>
</author>
</analytic>
</biblStruct>
<biblStruct><analytic><author><name sortKey="Vriezinga, Sl" uniqKey="Vriezinga S">SL Vriezinga</name>
</author>
<author><name sortKey="Auricchio, R" uniqKey="Auricchio R">R Auricchio</name>
</author>
<author><name sortKey="Bravi, E" uniqKey="Bravi E">E Bravi</name>
</author>
<author><name sortKey="Castillejo, G" uniqKey="Castillejo G">G Castillejo</name>
</author>
<author><name sortKey="Chmielewska, A" uniqKey="Chmielewska A">A Chmielewska</name>
</author>
<author><name sortKey="Crespo Escobar, P" uniqKey="Crespo Escobar P">P Crespo Escobar</name>
</author>
</analytic>
</biblStruct>
</listBibl>
</div1>
</back>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Genome Med</journal-id>
<journal-id journal-id-type="iso-abbrev">Genome Med</journal-id>
<journal-title-group><journal-title>Genome Medicine</journal-title>
</journal-title-group>
<issn pub-type="epub">1756-994X</issn>
<publisher><publisher-name>BioMed Central</publisher-name>
<publisher-loc>London</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26244058</article-id>
<article-id pub-id-type="pmc">4523954</article-id>
<article-id pub-id-type="publisher-id">196</article-id>
<article-id pub-id-type="doi">10.1186/s13073-015-0196-5</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research</subject>
</subj-group>
</article-categories>
<title-group><article-title>Genomic prediction of celiac disease targeting HLA-positive individuals</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0003-4853-0118</contrib-id>
<name><surname>Abraham</surname>
<given-names>Gad</given-names>
</name>
<address><email>gad.abraham@unimelb.edu.au</email>
</address>
<xref ref-type="aff" rid="Aff1"></xref>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rohmer</surname>
<given-names>Alexia</given-names>
</name>
<xref ref-type="aff" rid="Aff2"></xref>
<xref ref-type="aff" rid="Aff3"></xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Tye-Din</surname>
<given-names>Jason A.</given-names>
</name>
<xref ref-type="aff" rid="Aff4"></xref>
<xref ref-type="aff" rid="Aff5"></xref>
<xref ref-type="aff" rid="Aff6"></xref>
<xref ref-type="aff" rid="Aff7"></xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Inouye</surname>
<given-names>Michael</given-names>
</name>
<xref ref-type="aff" rid="Aff1"></xref>
<xref ref-type="aff" rid="Aff2"></xref>
</contrib>
<aff id="Aff1"><label></label>
Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville, 3010 Victoria Australia</aff>
<aff id="Aff2"><label></label>
Medical Systems Biology, Department of Pathology and Department of Microbiology & Immunology, The University of Melbourne, Parkville, 3010 Victoria Australia</aff>
<aff id="Aff3"><label></label>
Faculty of Life Science, University of Strasbourg, Strasbourg, 67084 CEDEX France</aff>
<aff id="Aff4"><label></label>
The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, 3052 Victoria Australia</aff>
<aff id="Aff5"><label></label>
Department of Medical Biology, The University of Melbourne, Parkville, 3010 Victoria Australia</aff>
<aff id="Aff6"><label></label>
Department of Gastroenterology, The Royal Melbourne Hospital, Grattan St., Parkville, 3050 Victoria Australia</aff>
<aff id="Aff7"><label></label>
Murdoch Children’s Research Institute, Flemington Road, Parkville, Victoria 3050 Australia</aff>
</contrib-group>
<pub-date pub-type="epub"><day>16</day>
<month>7</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>16</day>
<month>7</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection"><year>2015</year>
</pub-date>
<volume>7</volume>
<issue>1</issue>
<elocation-id>72</elocation-id>
<history><date date-type="received"><day>4</day>
<month>4</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>8</day>
<month>7</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© Abraham et al. 2015</copyright-statement>
<license license-type="open-access"><license-p><bold>Open Access</bold>
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/publicdomain/zero/1.0/">http://creativecommons.org/publicdomain/zero/1.0/</ext-link>
) applies to the data made available in this article, unless otherwise stated.</license-p>
</license>
</permissions>
<abstract id="Abs1"><sec><title>Background</title>
<p>Genomic prediction aims to leverage genome-wide genetic data towards better disease diagnostics and risk scores. We have previously published a genomic risk score (GRS) for celiac disease (CD), a common and highly heritable autoimmune disease, which differentiates between CD cases and population-based controls at a clinically-relevant predictive level, improving upon other gene-based approaches. HLA risk haplotypes, particularly HLA-DQ2.5, are necessary but not sufficient for CD, with at least one HLA risk haplotype present in up to half of most Caucasian populations. Here, we assess a genomic prediction strategy that specifically targets this common genetic susceptibility subtype, utilizing a supervised learning procedure for CD that leverages known HLA-DQ2.5 risk.</p>
</sec>
<sec><title>Methods</title>
<p>Using L1/L2-regularized support-vector machines trained on large European case-control datasets, we constructed novel CD GRSs specific to individuals with HLA-DQ2.5 risk haplotypes (GRS-DQ2.5) and compared them with the predictive power of the existing CD GRS (GRS14) as well as two haplotype-based approaches, externally validating the results in a North American case-control study.</p>
</sec>
<sec><title>Results</title>
<p>Consistent with previous observations, both the existing GRS14 and the GRS-DQ2.5 had better predictive performance than the HLA haplotype approaches. GRS-DQ2.5 models, based on directly genotyped or imputed markers, achieved similar levels of predictive performance (AUC = 0.718-0.73), which were substantially higher than those obtained from the DQ2.5 zygosity alone (AUC = 0.558), the HLA risk haplotype method (AUC = 0.634), or the generic GRS14 (AUC = 0.679). In a screening model of at-risk individuals, the GRS-DQ2.5 lowered the number of unnecessary follow-up tests for CD across most sensitivity levels. Relative to a baseline implicating all DQ2.5-positive individuals for follow-up, the GRS-DQ2.5 resulted in a net saving of 2.2 unnecessary follow-up tests for each justified test while still capturing 90 % of DQ2.5-positive CD cases.</p>
</sec>
<sec><title>Conclusions</title>
<p>Genomic risk scores for CD that target genetically at-risk sub-groups improve predictive performance beyond traditional approaches and may represent a useful strategy for prioritizing individuals at increased risk of disease, thus potentially reducing unnecessary follow-up diagnostic tests.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s13073-015-0196-5) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
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