Screening of intracerebral hemorrhage associated allele combinations at different loci using a novel association analysis

• To screen intracerebral hemorrhage (CH) genes from analysing allele combinations
• Random distribution of pairwise combinations of alleles at different loci was tested.
• Age of disease onset for patients carrying specific gene combinations was observed.
• Cross-validation replaced Bonferroni's correction to identify CH-associated genes.
• An extensive number of micro-effective CH-associated genes may exist in the genome.

BackgroundGenetic research has progressed along with scientific and technological developments. However, it is difficult to identify frequency differences in the allele combination at cross-loci.ObjectiveThe purpose of this study was to examine the relationship between the presence of specific allele combinations of short tandem repeat (STR) loci and the onset of intracerebral hemorrhage (ICH) using a novel methodology.MethodsDNA samples were collected from patients with ICH, who were adult population. There were a total of 51 Chinese patients (102 chromosomes), comprising 30 males and 21 females. Alleles from short tandem repeat (STR) loci were determined using the STR Profiler Plus PCR amplification kit (15 STR loci). Statistically significant differences between observed and expected frequencies of allele combinations were identified. To further determine allele combinations related to the disease, analyses of patient age at disease onset for those carrying a specific allele combination were conducted. Finally, cross-validation of the two sets of analytical results was carried out.ResultsA total of 1550 pairwise combinations were obtained by computer counting, of which eight pairs of alleles showed significant differences between the observed and expected frequencies (p < 0.05, from 0.006 to 0.042). The p value for the cross-validation analysis was less than 0.05 for two pairs of alleles (D13S317-11 and vWA-17, p = 0.021; D7S820-13 and D2S1338-18, p = 0.023).ConclusionsThe study identified each population had a unique gene distribution and that distribution followed certain rules. ICH onset may be associated with this allele combinations (D13S317-11 and vWA-17; D7S820-13 and D2S1338-18). The new methodology used in this study could enable additional discoveries pertaining to the relationship between specific allele combinations at different loci and the onset of complex diseases.