Scientiic Journal of Genetics and Gene Therapy eertechz Citation: Mellerup E, Moeller GL, Mondal P, Roychoudhury S (2015) Combinations of Genetic Data Reveal Latent Information in a Study of Oral Cancer. Scientiic J Genetics Gen Ther 1(1): 007-011. 007 Abstract In the single locus strategy a number of genetic variants are analyzed, in order to ind variants that are distributed signiicantly different between controls and patients. A supplementary strategy can be based on the concept of a polygenic disorder, as a disorder where the genetic basis is a combination of genetic variants. This combination will not occur in control persons genetically unrelated to patients, so the strategy is to analyze combinations of genetic variants present exclusively in patients. In a previous study of oral cancer and leukoplakia 325 SNPs were analyzed. This study has been supplemented with an analysis of combinations of two SNP genotypes from among the 325 SNPs. The theoretical number of such combinations is 473,850. Control persons and patients contained 395,193 combinations, most of which were common for the two groups, but 46,469 combinations were found exclusively in patients. Two genetically very different subgroups of these patient-speciic combinations were signiicantly associated with oral cancer or leukoplakia. 55 per cent of the patients with oral cancer and 16 per cent of the patients with leukoplakia belonged to the two subgroups. 325 SNPs were analyzed, the SNPs were from a previous study of oral cancer and leukoplakia [14]. Materials and Methods SNP genotype data Procedures for collection of blood samples and written informed consent form were reviewed and approved by the Institutional Ethical Committee, CSRI-Indian Institute of Chemical Biology, Kolkata, India. Written informed consent was obtained from all case and control subjects. Subjects (535 control persons, 373 patients with oral cancer, 253 patients with leukoplakia), genes, SNP selection, and genotyping have previously been described in detail [14]. Combinations and statistics he theoretical number of combinations of two SNPs from among 325 SNPs is 325!/(325-2)!2! = 52,650. he theoretical number of combinations of two SNP genotypes from among 325 SNP is 52,650 x 3 2 = 473,850 because each SNP corresponds to three genotypes, and each combination of two SNPs corresponds to 3 2 combinations of two SNP genotypes. Preparation of data he SNP genotypes of control subjects and patients are listed in a Table 1 with 1161 rows (373 for patients with oral cancer + 253 for patients with leukoplakia + 535 for controls) and 325 columns ( for the SNPs). Analysis of combinations of two SNP genotypes Each of the 52,650 SNP pairs is analyzed one at a time. For Introduction A speciic combination of genetic changes is the genetic basis for a polygenic disorder; this combination can be found in patients, but not in control subjects genetically unrelated to patients, hereby, making it worthwhile to analyze combinations occurring exclusively in patients. If the disorder shows genetic heterogeneity several combinations of genetic variants may be basis for the disorder. Molecular genetic studies of many diseases have identiied a number of individual genetic variants contributing to the risk of disease. he efect size for most of these variants is small, which has led to the concept of missing heritability [1]. he explanation for missing heritability may be as-yet undiscovered genetic variants, but it may also be due to the lack of analysis of combinations of genetic variants, because the single variant in the combinations has a small efect and may not be identiied using a single locus strategy, although combinations of these variants may be signiicantly associated to the disorder. However, studies of combinations of genetic variants are rare, probably because of the computational and statistical challenges created by the large number of possible combinations, even with moderate numbers of genetic variants [2]. his problem can be addressed by restricting the analysis to a small number of genetic variants [3,4], by development of fast data mining methods [5-7], and by using specialized hardware, as multiple graphical processing units, to increase scanning speed [8,9]. Using such types of methods combinations of genetic variants have been analyzed in studies of esophageal cancer [10], bipolar disorder [11], neuroblastoma [12], and breast cancer [13]. In the present study combinations of two single nucleotide polymorphism (SNP) genotypes taken from among Research Article Combinations of Genetic Data Reveal Latent Information in a Study of Oral Cancer Erling Mellerup 1 *, Gert Lykke Moeller 2 , Pinaki Mondal 3 and Susanta Roychoudhury 4 1 Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, Faculty of Health, University of Copenhagen, Denmark 2 Genokey ApS, ScionDTU, Technical University of Denmark, Hoersholm, Denmark 3 National Brain Research Centre, Gurgaon, India 4 Cancer Biology and Inlammatory Disorder Division, CSIR- Indian Institute of Chemical Biology, Kolkata, India Dates: Received: 18 February, 2015; Accepted: 20 March, 2015; Published: 22 March, 2015 *Corresponding author: Erling Mellerup. Laboratory of Neuropsychiatry, Department of Neuroscience and Pharmacology, Faculty of Health, University of Copenhagen, Blegdamsvej 9, RH afsn, 6102, 2100, Copenhagen, Denmark, Tel: +45-39648415; E-mail: mellerup@sund.ku.dk www.peertechz.com Keywords: Combinations; Genetic data; Oral cancer