Genome‐wide association study of insect bite hypersensitivity in Dutch Shetland pony mares

Insect bite hypersensitivity (IBH) is the most common allergic disease present in horses worldwide. It has been shown that IBH is under genetic control, but the knowledge of associated genes is limited. We conducted a genome‐wide association study to identify and quantify genomic regions contributing to IBH in the Dutch Shetland pony population. A total of 97 cases and 91 controls were selected and matched on withers height, coat colour and pedigree to minimise the population stratification. A blood sample was collected from participating Shetland pony mares, their IBH phenotype was scored and the owner filled in a questionnaire. A total of 40 021 single‐nucleotide polymorphisms (SNPs) were fitted in a univariable logistic model fitting an additive effect. Analysis revealed no effects of population stratification. Significant associations with IBH were detected for 24 SNPs on 12 chromosomes [?log₁₀(P‐value) > 2.5]. Odds ratios of allele substitution effects of the unfavourable allele were between 1.94 and 5.95. The most significant SNP was found on chromosome 27, with an odds ratio of 2.31 and with an allele frequency of the unfavourable allele of 0.72 in cases and 0.53 in controls. Genome‐wide association studies on additional horse populations are desired to validate the identified associations, to identify the genes involved in IBH and to develop genomic tools to decrease IBH prevalence.     

Association of ATM and BMI‐1 genetic variation with breast cancer risk in Han Chinese

We tested the hypothesis that genetic variation in ATM and BMI‐1 genes can alter the risk of breast cancer through genotyping 6 variants among 524 breast cancer cases and 518 cancer‐free controls of Han nationality. This was an observational, hospital‐based, case–control association study. Analyses of single variant, linkage, haplotype, interaction and nomogram were performed. Risk was expressed as odds ratio (OR) and 95% confidence interval (CI). All studied variants were in the Hardy‐Weinberg equilibrium and were not linked. The mutant allele frequencies of rs1890637, rs3092856 and rs1801516 in ATM gene were significantly higher in cases than in controls (P = .005, <.001 and .001, respectively). Two variants, rs1042059 and rs201024480, in BMI‐1 gene were low penetrant, with no detectable significance. After adjustment, rs189037 and rs1801516 were significantly associated with breast cancer under the additive model (OR: 1.37 and 1.52, 95% CI: 1.10‐1.71 and 1.14‐2.04, P: .005 and .005, respectively). In haplotype analysis, haplotypes A‐C‐G‐G (in order of rs189037, rs3092856, rs1801516 and rs373759) and A‐C‐A‐A in ATM gene were significantly associated with 1.98‐fold and 6.04‐fold increased risk of breast cancer (95% CI: 1.36‐2.90 and 1.65‐22.08, respectively). Nomogram analysis estimated that the cumulative proportion of 3 significant variants in ATM gene was about 12.5%. Our findings collectively indicated that ATM gene was a candidate gene in susceptibility to breast cancer in Han Chinese.     

Replication of an association of variation in the FOXO3A gene with human longevity using both case–control and longitudinal data

Genetic variation in FOXO3A has previously been associated with human longevity. Studies published so far have been case–control studies and hence vulnerable to bias introduced by cohort effects. In this study we extended the previous findings in the cohorts of oldest old Danes (the Danish 1905 cohort, N = 1089) and middle‐aged Danes (N = 736), applying a longitudinal study design as well as the case–control study design. Fifteen SNPs were chosen in order to cover the known common variation in FOXO3A. Comparing SNP frequencies in the oldest old with middle‐aged individuals, we found association (after correction for multiple testing) of eight SNPs; 4 (rs13217795, rs2764264, rs479744, and rs9400239) previously reported to be associated with longevity and four novel SNPs (rs12206094, rs13220810, rs7762395, and rs9486902 (corrected P‐values 0.001–0.044). Moreover, we found association of the haplotypes TAC and CAC of rs9486902, rs10499051, and rs12206094 (corrected P‐values: 0.01–0.03) with longevity. Finally, we here present data applying a longitudinal study design; when using follow‐up survival data on the oldest old in a longitudinal analysis, we found no SNPs to remain significant after the correction for multiple testing (Bonferroni correction). Hence, our results support and extent the proposed role of FOXO3A as a candidate longevity gene for survival from younger ages to old age, yet not during old age.