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Aims: Statin-related myopathy (SRM), which includes rhabdomyolysis, is an uncommon but important adverse drug reaction because the number of people prescribed statins world-wide is large. Previous association studies of common genetic variants have had limited success in identifying a genetic basis for this adverse drug reaction. We conducted a multi-site whole-exome sequencing study to investigate whether rare coding variants confer an increased risk of SRM. Methods and results: SRM 3–5 cases (N = 505) and statin treatment-tolerant controls (N = 2047) were recruited from multiple sites in North America and Europe. SRM 3–5 was defined as symptoms consistent with muscle injury and an elevated creatine phosphokinase level >4 times upper limit of normal without another likely cause of muscle injury. Whole-exome sequencing and variant calling was coordinated from two analysis centres, and results of single-variant and gene-based burden tests were meta-analysed. No genome-wide significant associations were identified. Given the large number of cases, we had 80% power to identify a variant with minor allele frequency of 0.01 that increases the risk of SRM 6-fold at genome-wide significance. Conclusions: In this large whole-exome sequencing study of severe statin-related muscle injury conducted to date, we did not find evidence that rare coding variants are responsible for this adverse drug reaction. Larger sample sizes would be required to identify rare variants with small effects, but it is unclear whether such findings would be clinically actionable. [ABSTRACT FROM AUTHOR]

Highly pathogenic avian influenza (HPAI) H5N1 continues to threaten domestic and wild birds, as well as human health. However, the mechanism of spatial transmission of HPAI is still unclear. We analyzed the current distribution of HPAI occurrences based on World Organization for Animal Health reported data from 3049 sites in the world from December 2003 to June 2006, and found that these sites were spaced at distances with a frequency peak of 100-200 km. We built a cellular automata model to simulate the spatial transmission process of HPAI as a function of transmission distance, variance of the transmission distance, infection rate, and transmission times (how many times HPAI transmits from one host to another before suppression). We determined that the transmission distance between HPAI occurrences is approximately 100 km on the basis of historical HPAI occurrences from 2003 to 2006 in both wild and domestic birds. To effectively reduce the long-distance spreading of HPAI, preventing close contact between domestic birds and waterfowl within a radius of 100 km around HPAI occurrence sites is essential., (© 2009 ISZS, Blackwell Publishing and IOZ/CAS.)