Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

Cervical spine injuries sustained by motorcyclists in road crashes in Malaysia

This study looks at cervical spine injuries sustained by motorcyclists in motorcycle road crashes. The motorcyclist is relatively more exposed to road hazards compared to the protected car passenger. They are therefore more prone to injury than those traveling in any other form of transportation. The motorcycle is relatively less stable and accords little protection to passengers in road crashes compared to a four-wheeled vehicle. The cause of injury and injury mechanisms are more uncertain for a motorcyclist compared to a car driver. The objective of the present study is to correlate the motorcycle crash mode to the cervical injury sustained by motorcyclists in real-world scenes. Motorcyclists with cervical injuries admitted to the hospitals were selected for investigation. The types of injuries sustained were acquired from medical reports. Information on the crash scene and crash mode was obtained from police reports and interview sessions arranged with the motorcyclists involved in the crash. Generally, a high count was noted for injuries to the lower cervical vertebrae, especially at vertebrae C5, intervertebral C5-C6, and vertebrae C6. The upper cervical spine was observed to have a high frequency of injury at C2, especially the odontoid process. Statistical analysis reveals that the vehicle crash mode is significant in determining the cervical injury mechanism sustained by motorcyclists (p < 0.05), and thus basic injury types sustained. Neck flexion and extension movements are the most frequent neck injury mechanisms, especially in frontal and rear end impacted motorcycles. Burst fractures were commonly observed in frontal impacts, while side impact and skidding motorcyclists were found to have a high frequency of uncinate process fractures, a result of neck lateral flexion. At the end of the study, a logistic regression model was developed. The model is simple and may be referred by paramedics in making any prompt prediction related to neck injury of motorcyclist due to road crash

Mechanisms of Cervical Spine Injuries for Non-Fatal Motorcycle Road Crash

Survival spine injuries such as subluxation and fracture dislocation have long been known to result in severe consequences, as well as the trauma management itself. The injury to the region to the region has been identified as one of the major causes of death in Malaysian motorcycle involved in road crashes, besides head and chest injuries (Pang, 1999). Despite this, cervical spine injury in motorcyclists it not a well-studied injury, unlike the whiplash injury in motorcar incidents. The present study is a retrospective study of the mechanism of injury in cervical spine sustained by Malaysian motorcyclists, who were involved in road crash using an established mechanistic classification system. This will serve as an initial step to look at the cervical injuries pattern, the information obtained gives engineer ideas to facilities design and safety features to reduce injuries. All cervical spine injured motorcyclists admitted to Hospital Kuala Lumpur between January 1, 2000 and December 31, 2001 were included in the present study. Based on the medical notes and radiological investigations (X-rays, CT and MRI scans), the mechanisms of injuries were formulated using the injury mechanisms classification. The result shows that flexion of the cervical vertebrae is the most common vertebral kinematics in causing injury to motorcyclists. This indicates that the cervical vertebrae sustained a high-energy loading at flexion movement in road crash, and exceeded its tolerance level. This high frequency of injury at the C5 vertebra and C5-C6 intervertebral space are recorded. Classification based on the Abbreviated Scale (AIS) is made to give a view on injury severity, 9.1% of the study samples have been classified as AIS code 1, 51.5% with AIS and 21.2% with AIS

Report of rare genotypes of Acanthamoeba from soil source of the Payeh Maga Highland forest, North-eastern Sarawak, Malaysia

Pathogenic Acanthamoeba species are the causative agents of Acanthamoeba keratitis and granulomatous amoebic encephalitis. Members of this amoeba genus are ubiquitous in the environments. In Malaysia, most environmental studies performed to date have targeted the detection and characterisation of Acanthamoeba sp. in different water sources, dust and soil samples collected near human habitats. However, no local study has yet to examine these amoebae in a forest, an isolated terrestrial environment, where human activity is relatively scarce. Further, there are also limited studies to investigate the same globally. The current study reported the isolation, morphological and genotypic characterisations of eleven Acanthamoeba sp. isolated from soils of the Payeh Maga Highland forest, Sarawak, Malaysia. Morphological analysis revealed that nine isolates belonged to Group II, whereas two isolates belonged to Group III as defined by the criteria of Pussard and Pons. The phylogenetic analysis based on complete 18S rRNA gene sequences showed that the isolates belonged to the rare T1 (six isolates), T6 (two isolates) and T13 (three isolates) genotypes. To the best of our knowledge, this is the first report about the detection of T6 Acanthamoeba sp. in this country. Overall, the current findings have enriched the knowledge pertaining to the occurrence, morphological and genotypic characteristics of Acanthamoeba sp. in an isolated terrestrial environment of Malaysia

Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.

Acknowledgements: This research was supported primarily by US National Institutes of Health (NIH) grant R01CA188214 (to W.Z.), Anne Potter Wilson Chair endowment from the Vanderbilt University School of Medicine (to W.Z.), and NIH grant R37CA227130 and R01CA269589 (to X.G.). Sample preparation and genotyping assays at Vanderbilt University were conducted at the Survey and Biospecimen Shared Resources and Vanderbilt Microarray Shared Resource, supported in part by the Vanderbilt-Ingram Cancer Center (grant P30CA068485). Data analyses were performed on servers maintained by the Advanced Computing Center for Research and Education (ACCRE) at Vanderbilt University.Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

Observing and understanding the Southeast Asian aerosol system by remote sensing: An initial review and analysis for the Seven Southeast Asian Studies (7SEAS) program

10.1016/j.atmosres.2012.06.005Atmospheric Research122403-46