TY - JOUR
T1 - Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia
AU - The International Schizophrenia Consortium
AU - Chen, Jingchun
AU - Lee, Grace
AU - Fanous, Ayman H.
AU - Zhao, Zhongming
AU - Jia, Peilin
AU - O'neill, Anthony
AU - Walsh, Dermot
AU - Kendler, Kenneth S.
AU - Chen, Xiangning
AU - O’Donovan, Michael C.
AU - Kirov, George K.
AU - Craddock, Nick J.
AU - Holmans, Peter A.
AU - Williams, Nigel M.
AU - Georgieva, Lyudmila
AU - Nikolov, Ivan
AU - Norton, N.
AU - Williams, H.
AU - Toncheva, Draga
AU - Milanova, Vihra
AU - Owen, Michael J.
AU - Hultman, Christina M.
AU - Lichtenstein, Paul
AU - Thelander, Emma F.
AU - Sullivan, Patrick
AU - Morris, Derek W.
AU - O’Dushlaine, Colm T.
AU - Kenny, Elaine
AU - Quinn, Emma M.
AU - Gill, Michael
AU - Corvin, Aiden
AU - McQuillin, Andrew
AU - Choudhury, Khalid
AU - Datta, Susmita
AU - Pimm, Jonathan
AU - Thirumalai, Srinivasa
AU - Puri, Vinay
AU - Krasucki, Robert
AU - Lawrence, Jacob
AU - Quested, Digby
AU - Bass, Nicholas
AU - Gurling, Hugh
AU - Crombie, Caroline
AU - Fraser, Gillian
AU - Kuan, Soh Leh
AU - Walker, Nicholas
AU - St Clair, David
AU - Blackwood, Douglas H.R.
AU - Muir, Walter J.
AU - McGhee, Kevin A.
AU - Pickard, Ben
AU - Malloy, Pat
AU - Maclean, Alan W.
AU - Van Beck, Margaret
AU - Wray, Naomi R.
AU - Macgregor, Stuart
AU - Visscher, Peter M.
AU - Pato, Michele T.
AU - Medeiros, Helena
AU - Middleton, Frank
AU - Carvalho, Celia
AU - Morley, Christopher
AU - Fanous, Ayman
AU - Conti, David
AU - Knowles, James A.
AU - Paz Ferreira, Carlos
AU - Macedo, Antonio
AU - Helena Azevedo, M.
AU - Pato, Carlos N.
AU - Stone, Jennifer L.
AU - Ruderfer, Douglas M.
AU - Kirby, Andrew N.
AU - Ferreira, Manuel A.R.
AU - Daly, Mark J.
AU - Purcell, Shaun M.
AU - Sklar, Pamela
AU - Stone, Jennifer L.
AU - Chambert, Kimberly
AU - Kuruvilla, Finny
AU - Gabriel, Stacey B.
AU - Ardlie, Kristin
AU - Moran, Jennifer L.
AU - Scolnick, Edward M.
PY - 2011/9/1
Y1 - 2011/9/1
N2 - We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r2>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10×10-3 and rs2274736, P=1.21×10-3). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45×10-3 and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29×10-3). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43×10-3). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.
AB - We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r2>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10×10-3 and rs2274736, P=1.21×10-3). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45×10-3 and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29×10-3). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43×10-3). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.
KW - Data-mining
KW - Genetic association study
KW - Informatic prioritization
KW - Non-synonymous snp
KW - PTPN21
UR - https://www.scopus.com/pages/publications/80051782509
U2 - 10.1016/j.schres.2011.06.023
DO - 10.1016/j.schres.2011.06.023
M3 - Article
AN - SCOPUS:80051782509
SN - 0920-9964
VL - 131
SP - 43
EP - 51
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 1-3
ER -