期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 73, 期 1, 页码 34-48出版社
CELL PRESS
DOI: 10.1086/376549
关键词
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资金
- Medical Research Council [G9309834, G9810900] Funding Source: researchfish
- MRC [G9810900, G9309834] Funding Source: UKRI
- Medical Research Council [G9309834, G9810900] Funding Source: Medline
- NIMH NIH HHS [R01 MH062440, U01 MH 44292, R01 MH 61602, 1R37 MH 43518, K24 MH064197, U01 MH046318, R01 MH 4558, K02 MH 01089, R01 MH 52537, U01 MH046276, R01 MH044292, R01 MH 45390, 5U01 MH 46318, R01 MH 44245, U01 MH 46289, R01 MH041953, R01 MH 41953, K08 MH 01392, R01 MH 56098, U01 MH046289, U01 MH 46276, R01 MH 45097, 1R01 MH 41874-01, R01 MH 62440, R37 MH043518, R01 MH 42643, K24 MH 64197] Funding Source: Medline
- PHS HHS [K02 01207] Funding Source: Medline
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 (R-avg) and then weighted for sample size (rootN[affected cases]). A permutation test was used to compute the probability of observing, by chance, each bin's average rank (P-AvgRnk) or of observing it for a bin with the same place (first, second, etc.) in the order of average ranks in each permutation (P-ord). The GSMA produced significant genomewide evidence for linkage on chromosome 2q (P-AvgRnk <.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 P-AvgRnk and P-ord <.05, including regions of chromosomes 5q, 3p, 11q, 6p, 1q, 22q, 8p, 20q, and 14p, and 19 consecutive bins with, 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.
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