Chen, Wei
Mayo Clinic
The University of Texas MD Anderson Cancer Center
Citations 2
Genome‐Wide Association Study of Dermatomyositis Reveals Genetic Overlap With Other Autoimmune Disorders
Miller, Frederick W. , Vencovský, Jiří , Rider, Lisa G. , Dankó, Katalin , Wedderburn, Lucy R. , Lundberg, Ingrid E. , Pachman, Lauren M. , Reed, Ann M. , Ytterberg, Steven R. , Padyukov, Leonid , Selva-O’Callaghan, Albert , Radstake, Timothy R. D. J., Isenberg, David , Chinoy, Hector , Ollier, William , OʼHanlon, Terrance P., Peng, Bo , Lee, Annette , Lamb, Janine A. , Gregersen, Peter K., Lanyon, Peter , Cooper, Robert G. , Chen, Wei , Amos, Christopher I. , Vencovsky, Jiri , Isenberg, David A , Padyukov, Leonid , Chinoy, Hector , Selva O'Callaghan, Albert , Lamb, Janine A , Lundberg, Ingrid E
Arthritis & Rheumatism | August 27, 2013 | Volume: 65 | Issue: 12 | Pages: 3239-3247
ObjectiveTo identify new genetic associations with juvenile and adult dermatomyositis (DM).MethodsWe performed a genome‐wide association study (GWAS) of adult and juvenile DM patients of European ancestry (n = 1,178) and controls (n = 4,724). To assess genetic overlap with other autoimmune disorders, we examined whether 141 single‐nucleotide polymorphisms (SNPs) outside the major histocompatibility complex (MHC) locus, and previously associated with autoimmune diseases, predispose to DM.ResultsCompared to controls, patients with DM had a strong signal in the MHC region consisting of GWAS‐level significance (P < 5 × 10–8) at 80 genotyped SNPs. An analysis of 141 non‐MHC SNPs previously associated with autoimmune diseases showed that 3 SNPs linked with 3 genes were associated with DM, with a false discovery rate (FDR) of <0.05. These genes were phospholipase C–like 1 (PLCL1; rs6738825, FDR = 0.00089), B lymphoid tyrosine kinase (BLK; rs2736340, FDR = 0.0031), and chemokine (C‐C motif) ligand 21 (CCL21; rs951005, FDR = 0.0076). None of these genes was previously reported to be associated with DM.ConclusionOur findings confirm the MHC as the major genetic region associated with DM and indicate that DM shares non‐MHC genetic features with other autoimmune diseases, suggesting the presence of additional novel risk loci. This first identification of autoimmune disease genetic predispositions shared with DM may lead to enhanced understanding of pathogenesis and novel diagnostic and therapeutic approaches.
Genetic variants near TIMP3 and high-density lipoprotein–associated loci influence susceptibility to age-related macular degeneration
Stambolian, Dwight, Edwards, Albert O., Branham, Kari , Othman, Mohammad , Jakobsdóttir, Jóhanna , Tosakulwong, Nirubol , Pericak‐Vance, Margaret A. , Klein, Michael L. , Tan, Perciliz L. , Kanda, Atsuhiro , Kopplin, Laura J. , Li, Yanming , Augustaitis, Katherine J., Karoukis, Athanasios J., Scott, William K. , Agarwal, Anita , Kovach, Jaclyn L. , Postel, Eric A. , Brooks, Matthew, Baratz, Keith H. , Brown, William L. , Brucker, Alexander J., Orlin, Anton, Brown, Gary C. , Ho, Allen C. , Regillo, Carl D. , Donoso, Larry A., Tian, Lifeng , Kaderli, Brian, Hadley, Dexter , Hagstrom, Stephanie A. , Peachey, Neal S. , Klein, Ronald , Klein, Barbara E.K. , Gotoh, Norimoto, Yamashiro, Kenji , Ferris, Frederick L. , Fagerness, Jesen, Reynolds, Robyn, Farrer, Lindsay A. , Kim, Ivana K. , Miller, Joan W. , Cortón, Marta , Carracedo, Ãngel , Sánchez‐Salorio, Manuel, Pugh, Elizabeth, Doheny, Kimberly F. , Brión, Marı́a , Weeks, Daniel E. , Zack, Donald J. , Heckenlively, John R., Yoshimura, Nagahisa , Iyengar, Sudha K. , Francis, Peter J. , Katsanis, Nicholas , Seddon, Johanna M. , Haines, Jonathan L. , Abecasis, Gonçalo R. , Swaroop, Anand , Johnson, Robert N., Ai, Everett, McDonald, H. Richard , Stolarczuk, Margaret, Pavan, Peter R., Billiris, Karina K., Iyer, Mohan , Menosky, Matthew M., Pautler, Scott E. , Millard, Sharon M., Hubbard, G. Baker , Aaberg, Thomas , DuBois, Lindy, Lyon, Alice T., Anderson-Nelson, Susan, Jampol, Lee M. , Muñana, Annie, Rozenbajgier, Zuzanna, Orth, David H., Cohen, Jack, MacCumber, Matthew, Figliulo, Celeste, Porcz, Liz, Folk, James C. , Boldt, H. Culver , Russell, Stephen R. , Ivins, Rachel, Hinz, Connie J., Bloom, Steve, Jaegers, Ken, Kritchman, Brian, Whittington, Greg K., Frederick, Albert R., Morley, Michael G., Topping, Trexler M., Davis, Heather L., Bressler, Susan B., Bressler, Neil M. , Doll, W T Jr, Trese, Michael T. , Garretson, Bruce R., Ruby, Alan, Osentoski, Tammy, Ruszczyk, Margaret, Grand, G., Joseph, Daniel P., Shah, Gaurav K. , Nobel, Ginny, Antoszyk, Andrew N., Stallings, Alison H, Singerman, Lawrence J. , Miller, David T. , Novák, Michael, Pendergast, Scott, Zegarra, Hernando, Schura, Stephanie A., Smith-Brewer, Sheila, Davidorf, Frederick H., Chorich, Louis J., Salerno, Jill, Dreyer, Richard F., Ma, Colin, Kopfer, Marcia, Wilson, David J. , Nolte, Susan K., Grunwald, Juan E. , Dunaief, Josh, Fine, Stuart L., Maguire, Albert M. , Stoltz, Robert A., McRay, Monique, Fish, Gary E., Anand, Rajiv, Spencer, Rand , Arnwine, Jean, Chandra, Suresh R., Blodi, Barbara, Gottlieb, Justin L., Ip, Michael S. , Nork, T. Michael , Perry-Raymond, Jennie, Brightwell-Arnold, Mary, Harkins, Sandra, Peskin, Ellen, Ying, Gui‐Shuang , Kurinij, Natalie, Chen, Wei , Campochiaro, Peter A. , Conley, Yvette P. , Schwartz, Stephen G. , DeAngelis, Margaret M. , Chew, Emily Y. , Gorin, Michael B. , Menosky, Matthew M., Weinberg, David V. , Barr, Charles C. , Heier, Jeffrey S. , Capone, A. , Hassan, T. , McCannel, Colin A. , Blinder, Kevin J. , Holekamp, Nancy M. , Browning, David J. , Chambers, Robert , Altaweel, Michael M. , Maguire, Maureen G. , Weeks, Daniel E , Brion, María , Abecasis, Gonçalo
Proceedings of the National Academy of Sciences | April 12, 2010 | Volume: 107 | Issue: 16 | Pages: 7401-7406
We executed a genome-wide association scan for age-related macular degeneration (AMD) in 2,157 cases and 1,150 controls. Our results validate AMD susceptibility loci near CFH ( P < 10 −75 ), ARMS2 ( P < 10 −59 ), C2/CFB ( P < 10 −20 ), C3 ( P < 10 −9 ), and CFI ( P < 10 −6 ). We compared our top findings with the Tufts/Massachusetts General Hospital genome-wide association study of advanced AMD (821 cases, 1,709 controls) and genotyped 30 promising markers in additional individuals (up to 7,749 cases and 4,625 controls). With these data, we identified a susceptibility locus near TIMP3 (overall P = 1.1 × 10 −11 ), a metalloproteinase involved in degradation of the extracellular matrix and previously implicated in early-onset maculopathy. In addition, our data revealed strong association signals with alleles at two loci ( LIPC , P = 1.3 × 10 −7 ; CETP , P = 7.4 × 10 −7 ) that were previously associated with high-density lipoprotein cholesterol (HDL-c) levels in blood. Consistent with the hypothesis that HDL metabolism is associated with AMD pathogenesis, we also observed association with AMD of HDL-c—associated alleles near LPL ( P = 3.0 × 10 −3 ) and ABCA1 ( P = 5.6 × 10 −4 ). Multilocus analysis including all susceptibility loci showed that 329 of 331 individuals (99%) with the highest-risk genotypes were cases, and 85% of these had advanced AMD. Our studies extend the catalog of AMD associated loci, help identify individuals at high risk of disease, and provide clues about underlying cellular pathways that should eventually lead to new therapies.