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- Guo, Xingyi, et al.
(författare)
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Identifying Novel Susceptibility Genes for Colorectal Cancer Risk From a Transcriptome-Wide Association Study of 125,478 Subjects
- 2020
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Ingår i: Gastroenterology. - : Elsevier. - 0016-5085 .- 1528-0012. ; 160:4, s. 1164-1178
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Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Susceptibility genes and the underlying mechanisms for the majority of risk loci identified by genome-wide association studies (GWAS) for colorectal cancer (CRC) risk remain largely unknown. We conducted a transcriptome-wide association study (TWAS) to identify putative susceptibility genes.Methods: Gene-expression prediction models were built using transcriptome and genetic data from the 284 normal transverse colon tissues of European descendants from the Genotype-Tissue Expression (GTEx), and model performance was evaluated using data from The Cancer Genome Atlas (n = 355). We applied the gene-expression prediction models and GWAS data to evaluate associations of genetically predicted gene-expression with CRC risk in 58,131 CRC cases and 67,347 controls of European ancestry. Dual-luciferase reporter assays and knockdown experiments in CRC cells and tumor xenografts were conducted.Results: We identified 25 genes associated with CRC risk at a Bonferroni-corrected threshold of P < 9.1 × 10-6, including genes in 4 novel loci, PYGL (14q22.1), RPL28 (19q13.42), CAPN12 (19q13.2), MYH7B (20q11.22), and MAP1L3CA (20q11.22). In 9 known GWAS-identified loci, we uncovered 9 genes that have not been reported previously, whereas 4 genes remained statistically significant after adjusting for the lead risk variant of the locus. Through colocalization analysis in GWAS loci, we additionally identified 12 putative susceptibility genes that were supported by TWAS analysis at P < .01. We showed that risk allele of the lead risk variant rs1741640 affected the promoter activity of CABLES2. Knockdown experiments confirmed that CABLES2 plays a vital role in colorectal carcinogenesis.Conclusions: Our study reveals new putative susceptibility genes and provides new insight into the biological mechanisms underlying CRC development.
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| 2. |
- Lin, Weiqiang, et al.
(författare)
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Migration infrastructures and the production of migrant mobilities
- 2017
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Ingår i: Mobilities. - : Informa UK Limited. - 1745-0101 .- 1745-011X. ; 12:2, s. 167-174
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Tidskriftsartikel (refereegranskat)abstract
- Since the proclamation of a mobility turn in the 2000s, scholars have populated the field with invaluable insights on what it means to move, and what the politics of movement are. One particularly useful thread revolves around the issue of infrastructures, which have generally been taken to mean the manifest forms of moorings and fixities that help order and give shape to mobilities. Yet, while significant inroads have been made in delineating the morphologies of transport infrastructures, mobilities research has been relatively reticent about the organisational structures, orders and arrangements that give rise to another key mobile phenomenon of our time international migration. In this editorial introduction, we lay down some groundwork on the productive and political nature of infrastructures that likewise affect and inform the way (im)mobilities are contingently created and parsed in migration. Looking through the prism of East and Southeast Asia and its migration infrastructures, we take advantage of the new' infrastructural configurations in an emerging empirical context to point to some directions by which mobilities researchers can more rigorously interrogate migration' as another socially meaningful and specific form of mobility that exceeds a mere displacement of people or change in national domicile.
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