TY - JOUR
T1 - Genome scan meta-analysis of schizophrenia and bipolar disorder, part II
T2 - Schizophrenia
AU - Lewis, Cathryn M.
AU - Levinson, Douglas F.
AU - Wise, Lesley H.
AU - DeLisi, Lynn E.
AU - Straub, Richard E.
AU - Hovatta, Iiris
AU - Williams, Nigel M.
AU - Schwab, Sibylle G.
AU - Pulver, Ann E.
AU - Faraone, Stephen V.
AU - Brzustowicz, Linda M.
AU - Kaufmann, Charles A.
AU - Garver, David L.
AU - Gurling, Hugh M.D.
AU - Lindholm, Eva
AU - Coon, Hilary
AU - Moises, Hans W.
AU - Byerley, William
AU - Shaw, Sarah H.
AU - Mesen, Andrea
AU - Sherrington, Robin
AU - O'Neill, F. Anthony
AU - Walsh, Dermot
AU - Kendler, Kenneth S.
AU - Ekelund, Jesper
AU - Paunio, Tiina
AU - Lönnqvist, Jouko
AU - Peltonen, Leena
AU - O'Donovan, Michael C.
AU - Owen, Michael J.
AU - Wildenauer, Dieter B.
AU - Maier, Wolfgang
AU - Nestadt, Gerald
AU - Blouin, Jean Louis
AU - Antonarakis, Stylianos E.
AU - Mowry, Bryan J.
AU - Silverman, Jeremy M.
AU - Crowe, Raymond R.
AU - Cloninger, C. Robert
AU - Tsuang, Ming T.
AU - Malaspina, Dolores
AU - Harkavy-Friedman, Jill M.
AU - Svrakic, Dragan M.
AU - Bassett, Anne S.
AU - Holcomb, Jennifer
AU - Kalsi, Gursharan
AU - McQuillin, Andrew
AU - Brynjolfson, Jon
AU - Sigmundsson, Thordur
AU - Petursson, Hannes
AU - Jazin, Elena
AU - Zoëga, Tomas
AU - Helgason, Tomas
PY - 2003/7/1
Y1 - 2003/7/1
N2 - Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (Ravg) and then weighted for sample size (√N[affected cases]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (PAvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (Pord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk < .000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both PAvgRnk and Pord < .05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with Pord < .05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
AB - Schizophrenia is a common disorder with high heritability and a 10-fold increase in risk to siblings of probands. Replication has been inconsistent for reports of significant genetic linkage. To assess evidence for linkage across studies, rank-based genome scan meta-analysis (GSMA) was applied to data from 20 schizophrenia genome scans. Each marker for each scan was assigned to 1 of 120 30-cM bins, with the bins ranked by linkage scores (1 = most significant) and the ranks averaged across studies (Ravg) and then weighted for sample size (√N[affected cases]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (PAvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (Pord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (PAvgRnk < .000417). Two aggregate criteria for linkage were also met (clusters of nominally significant P values that did not occur in 1,000 replicates of the entire data set with no linkage present): 12 consecutive bins with both PAvgRnk and Pord < .05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with Pord < .05, additionally including regions of chromosomes 16q, 18q, 10p, 15q, 6q, and 17q. There is greater consistency of linkage results across studies than has been previously recognized. The results suggest that some or all of these regions contain loci that increase susceptibility to schizophrenia in diverse populations.
UR - https://www.scopus.com/pages/publications/0038003196
U2 - 10.1086/376549
DO - 10.1086/376549
M3 - Article
C2 - 12802786
SN - 0002-9297
VL - 73
SP - 34
EP - 48
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 1
ER -