Association of genetic profiles to Crohn’s disease by linear combinations of single nucleotide polymorphisms

D’Addabbo, Annarita; Latiano, Anna; Palmieri, Orazio; Creanza, Maria Teresa; Maglietta, Rosalia; Annese, Vito; Ancona, Nicola

doi:10.1016/j.artmed.2008.07.012

« Previous Next »Artificial Intelligence in Medicine
Volume 46, Issue 2 , Pages 131-138, June 2009

Association of genetic profiles to Crohn’s disease by linear combinations of single nucleotide polymorphisms

Annarita D’Addabbo
- Istituto di Studi sui Sistemi Intelligenti per l’Automazione-C.N.R., Via Amendola 122/D-I, 70126 Bari, Italy
Anna Latiano
- Unità Operative di Gastroenterologia ed Endoscopia Digestiva, Ospedale IRCCS, “Casa Sollievo della Sofferenza”, Viale Cappuccini, 71013 San Giovanni Rotondo (FG), Italy
Orazio Palmieri
- Unità Operative di Gastroenterologia ed Endoscopia Digestiva, Ospedale IRCCS, “Casa Sollievo della Sofferenza”, Viale Cappuccini, 71013 San Giovanni Rotondo (FG), Italy
Maria Teresa Creanza
- Istituto di Studi sui Sistemi Intelligenti per l’Automazione-C.N.R., Via Amendola 122/D-I, 70126 Bari, Italy
Rosalia Maglietta
- Istituto di Studi sui Sistemi Intelligenti per l’Automazione-C.N.R., Via Amendola 122/D-I, 70126 Bari, Italy
Vito Annese
- Unità Operative di Gastroenterologia ed Endoscopia Digestiva, Ospedale IRCCS, “Casa Sollievo della Sofferenza”, Viale Cappuccini, 71013 San Giovanni Rotondo (FG), Italy
Nicola Ancona
- Istituto di Studi sui Sistemi Intelligenti per l’Automazione-C.N.R., Via Amendola 122/D-I, 70126 Bari, Italy
- Corresponding author. Tel.: +39 080 5929428; fax: +39 080 5929460.

Received 22 January 2008; received in revised form 21 July 2008; accepted 21 July 2008.

Summary

Motivations

A large number of single nucleotide polymorphisms (SNPs) are supposed to be involved in onset, differentiation and development of complex diseases. Univariate analysis is limited in studying complex traits since does not take into account gene–gene interaction, and the correlation of multiple SNPs with a specific phenotype. Moreover it might underestimate gene variants with weaker genetic contribution. Therefore more sophisticated techniques should be adopted when investigating the role of a panel of genetic markers in disease predisposition.

Methods

In this paper we describe a general method to simultaneously investigate the association between SNPs profile and Crohn’s disease (CD), by evaluating the susceptibility or protective role of single or groups of markers. As an association measure we adopted a weighted linear combination of SNPs in which suitable weighting vectors belonged to predefined and over-complete vocabularies of vectors (frames), or were determined by the data.

Results

The proposed method found a weighted linear combination of SNPs statistically associated to CD describing the role of the markers in the pathology. In particular, MCP1-A2518G gave the major contribution as protective locus, similarly to TNF-C857T, DLG5 rs124869, PTPN22 C1858T variants. The NFB 94ATTG variants was found to be irrelevant for CD. For the remaining markers, a susceptibility role was attributed also confirming that markers on CARD15 gene, in particular G908R and L1007fsinsC, are involved with CD to the same extent as FcGIIIA G559T and TNF-G308A. Moreover, an odds ratio of was assigned to this combination which is greater than the best odds ratio found in the single SNP analysis.

Conclusions

Our methodology allowed to statistically measure the association of a panel of SNPs with a specific phenotype. Therefore this approach could be suitable for a population screening program with simultaneous evaluation of a large set of gene polymorphims.

Keywords: Single nucleotide polymorphisms, Crohn’s disease, Regularized least square classifiers