Journal Articles

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    Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes.
    (Springer Nature, 2024-04-26) Chen Z; Guo X; Tao R; Huyghe JR; Law PJ; Fernandez-Rozadilla C; Ping J; Jia G; Long J; Li C; Shen Q; Xie Y; Timofeeva MN; Thomas M; Schmit SL; Díez-Obrero V; Devall M; Moratalla-Navarro F; Fernandez-Tajes J; Palles C; Sherwood K; Briggs SEW; Svinti V; Donnelly K; Farrington SM; Blackmur J; Vaughan-Shaw PG; Shu X-O; Lu Y; Broderick P; Studd J; Harrison TA; Conti DV; Schumacher FR; Melas M; Rennert G; Obón-Santacana M; Martín-Sánchez V; Oh JH; Kim J; Jee SH; Jung KJ; Kweon S-S; Shin M-H; Shin A; Ahn Y-O; Kim D-H; Oze I; Wen W; Matsuo K; Matsuda K; Tanikawa C; Ren Z; Gao Y-T; Jia W-H; Hopper JL; Jenkins MA; Win AK; Pai RK; Figueiredo JC; Haile RW; Gallinger S; Woods MO; Newcomb PA; Duggan D; Cheadle JP; Kaplan R; Kerr R; Kerr D; Kirac I; Böhm J; Mecklin J-P; Jousilahti P; Knekt P; Aaltonen LA; Rissanen H; Pukkala E; Eriksson JG; Cajuso T; Hänninen U; Kondelin J; Palin K; Tanskanen T; Renkonen-Sinisalo L; Männistö S; Albanes D; Weinstein SJ; Ruiz-Narvaez E; Palmer JR; Buchanan DD; Platz EA; Visvanathan K; Ulrich CM; Siegel E; Brezina S; Gsur A; Campbell PT; Chang-Claude J; Hoffmeister M; Brenner H; Slattery ML; Potter JD; Tsilidis KK; Schulze MB; Gunter MJ; Murphy N; Castells A; Castellví-Bel S; Moreira L; Arndt V; Shcherbina A; Bishop DT; Giles GG; Southey MC; Idos GE; McDonnell KJ; Abu-Ful Z; Greenson JK; Shulman K; Lejbkowicz F; Offit K; Su Y-R; Steinfelder R; Keku TO; van Guelpen B; Hudson TJ; Hampel H; Pearlman R; Berndt SI; Hayes RB; Martinez ME; Thomas SS; Pharoah PDP; Larsson SC; Yen Y; Lenz H-J; White E; Li L; Doheny KF; Pugh E; Shelford T; Chan AT; Cruz-Correa M; Lindblom A; Hunter DJ; Joshi AD; Schafmayer C; Scacheri PC; Kundaje A; Schoen RE; Hampe J; Stadler ZK; Vodicka P; Vodickova L; Vymetalkova V; Edlund CK; Gauderman WJ; Shibata D; Toland A; Markowitz S; Kim A; Chanock SJ; van Duijnhoven F; Feskens EJM; Sakoda LC; Gago-Dominguez M; Wolk A; Pardini B; FitzGerald LM; Lee SC; Ogino S; Bien SA; Kooperberg C; Li CI; Lin Y; Prentice R; Qu C; Bézieau S; Yamaji T; Sawada N; Iwasaki M; Le Marchand L; Wu AH; Qu C; McNeil CE; Coetzee G; Hayward C; Deary IJ; Harris SE; Theodoratou E; Reid S; Walker M; Ooi LY; Lau KS; Zhao H; Hsu L; Cai Q; Dunlop MG; Gruber SB; Houlston RS; Moreno V; Casey G; Peters U; Tomlinson I; Zheng W
    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.
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    Transcriptomic Identification of a Unique Set of Nodule-Specific Cysteine-Rich Peptides Expressed in the Nitrogen-Fixing Root Nodule of Astragalus sinicus
    (The American Phytopathological Society in cooperation with the International Society for Molecular Plant-Microbe Interactions, 2022-10-08) Wei F; Liu Y; Zhou D; Zhao W; Chen Z; Chen D; Li Y; Zhang X-X
    Legumes in the inverted repeat-lacking clade (IRLC) each produce a unique set of nodule-specific cysteine-rich (NCR) peptides, which act in concert to determine the terminal differentiation of nitrogen-fixing bacteroid. IRLC legumes differ greatly in their numbers of NCR and sequence diversity. This raises the significant question how bacteroid differentiation is collectively controlled by the specific NCR repertoire of an IRLC legume. Astragalus sinicus is an IRLC legume that forms indeterminate nodules with its microsymbiont Mesorhizobium huakuii 7653R. Here, we performed transcriptome analysis of root and nodule samples at 3, 7, 14, 28 days postinoculation with M. huakuii 7653R and its isogenic ∆bacA mutant. BacA is a broad-specificity peptide transporter required for the host-derived NCRs to target rhizobial cells. A total of 167 NCRs were identified in the RNA transcripts. Comparative sequence and electrochemical analysis revealed that A. sinicus NCRs (AsNCRs) are dominated by a unique cationic group (termed subgroup C), whose mature portion is relatively long (>60 amino acids) and phylogenetically distinct and possessing six highly conserved cysteine residues. Subsequent functional characterization showed that a 7653R variant harboring AsNCR083 (a representative of subgroup C AsNCR) displayed significant growth inhibition in laboratory media and formed ineffective white nodules on A. sinicus with irregular symbiosomes. Finally, bacterial two-hybrid analysis led to the identification of GroEL1 and GroEL3 as the molecular targets of AsNCR067 and AsNCR076. Together, our data contribute to a systematic understanding of the NCR repertoire associated with the A. sinicus and M. huakuii symbiosis.