Περίληψη:
A genome scan meta-analysis (GSMA) was carried out on 32 independent
genome-wide linkage scan analyses that included 3255 pedigrees with 7413
genotyped cases affected with schizophrenia (SCZ) or related disorders.
The primary GSMA divided the autosomes into 120 bins, rank-ordered the
bins within each study according to the most positive linkage result in
each bin, summed these ranks (weighted for study size) for each bin
across studies and determined the empirical probability of a given
summed rank (P-SR) by simulation. Suggestive evidence for linkage was
observed in two single bins, on chromosomes 5q (142-168 Mb) and 2q
(103-134 Mb). Genome-wide evidence for linkage was detected on
chromosome 2q (119-152 Mb) when bin boundaries were shifted to the
middle of the previous bins. The primary analysis met empirical criteria
for ‘aggregate’ genome-wide significance, indicating that some or all of
10 bins are likely to contain loci linked to SCZ, including regions of
chromosomes 1, 2q, 3q, 4q, 5q, 8p and 10q. In a secondary analysis of 22
studies of European-ancestry samples, suggestive evidence for linkage
was observed on chromosome 8p (16-33 Mb). Although the newer genome-wide
association methodology has greater power to detect weak associations to
single common DNA sequence variants, linkage analysis can detect diverse
genetic effects that segregate in families, including multiple rare
variants within one locus or several weakly associated loci in the same
region. Therefore, the regions supported by this meta-analysis deserve
close attention in future studies. Molecular Psychiatry (2009) 14,
774-785; doi:10.1038/mp.2008.135; published online 30 December 2008
Συγγραφείς:
Ng, M. Y. M.
Levinson, D. F.
Faraone, S. V.
Suarez, B. K.
and DeLisi, L. E.
Arinami, T.
Riley, B.
Paunio, T. and
Pulver, A. E.
Irmansyah
Holmans, P. A.
Escamilla, M. and
Wildenauer, D. B.
Williams, N. M.
Laurent, C.
Mowry, B. J.
and Brzustowicz, L. M.
Maziade, M.
Sklar, P.
Garver, D. L.
and Abecasis, G. R.
Lerer, B.
Fallin, M. D.
Gurling, H. M.
D.
Gejman, P. V.
Lindholm, E.
Moises, H. W.
Byerley, W.
and Wijsman, E. M.
Forabosco, P.
Tsuang, M. T.
Hwu, H-G and
Okazaki, Y.
Kendler, K. S.
Wormley, B.
Fanous, A.
Walsh,
D.
O'Neill, F. A.
Peltonen, L.
Nestadt, G.
Lasseter, V.
K.
Liang, K. Y.
Papadimitriou, G. M.
Dikeos, D. G. and
Schwab, S. G.
Owen, M. J.
O'Donovan, M. C.
Norton, N. and
Hare, E.
Raventos, H.
Nicolini, H.
Albus, M.
Maier, W.
and Nimgaonkar, V. L.
Terenius, L.
Mallet, J.
Jay, M. and
Godard, S.
Nertney, D.
Alexander, M.
Crowe, R. R. and
Silverman, J. M.
Bassett, A. S.
Roy, M-A
Merette, C. and
Pato, C. N.
Pato, M. T.
Roos, J. Louw
Kohn, Y. and
Amann-Zalcenstein, D.
Kalsi, G.
McQuillin, A.
Curtis, D. and
Brynjolfson, J.
Sigmundsson, T.
Petursson, H.
Sanders, A. R.
and Duan, J.
Jazin, E.
Myles-Worsley, M.
Karayiorgou, M. and
Lewis, C. M.
