Evolutionary evidence of the effect of rare variants on disease etiology

Gorlov IP, Gorlova OY, Frazier ML, Spitz MR, Amos CI. Evolutionary evidence of the effect of rare variants on disease etiology. The common disease/common variant hypothesis has been popular for describing the genetic architecture of common human diseases for several years. According to the originally stated hypothesis, one or a few common genetic variants with a large effect size control the risk of common diseases. A growing body of evidence, however, suggests that rare single‐nucleotide polymorphisms (SNPs), i.e. those with a minor allele frequency of less than 5%, are also an important component of the genetic architecture of common human diseases. In this study, we analyzed the relevance of rare SNPs to the risk of common diseases from an evolutionary perspective and found that rare SNPs are more likely than common SNPs to be functional and tend to have a stronger effect size than do common SNPs. This observation, and the fact that most of the SNPs in the human genome are rare, suggests that rare SNPs are a crucial element of the genetic architecture of common human diseases. We propose that the next generation of genomic studies should focus on analyzing rare SNPs. Further, targeting patients with a family history of the disease, an extreme phenotype, or early disease onset may facilitate the detection of risk‐associated rare SNPs.     

Modified forced expiration technique using expiratory resistance in adults with cystic fibrosis

Background

Participation in airway clearance techniques (ACT) is important to minimise development of irreversible airway obstruction in patients with cystic fibrosis (CF). Positive expiratory pressure (PEP) and expiratory resistance devices (ERD) are often used as they can improve collateral ventilation and aid in the shearing of mucus from airways. This project looked to identify whether utilising an ERD during a forced expiration technique (FET) improves ease of expectoration, sputum amount and coughing frequency in patients with CF.

Method

Patients with CF admitted for a respiratory exacerbation completed two sessions of 10 cycles of their usual ACT with half of the FET components performed with an ERD, half with FET alone.

Results

EOE, sputum wet weight, cough frequency and patient preference were similar between groups. Improved EOE without the ERD was found in participants who usually use PEP for their ACT regime.

Conclusion

Combining the FET with a PEP mask did not improve EOE and other outcomes in this small study. Investigating the efficacy of this technique within a larger population is warranted.