?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.title=A+Genome-Wide+Scan+for+Linkage+to+Chromosomal+Regions+in+382+Sibling+Pairs+with+Schizophrenia+or+Schizoaffective+Disorder&rft.creator=DeLisi%2C+Prof+LE&rft.creator=Shaw%2C+Dr+SH&rft.creator=Crow%2C+Prof+TJ&rft.creator=Shields%2C+Dr+G&rft.creator=Smith%2C+Ms+AB&rft.creator=Larach%2C+Dr+VW&rft.creator=Wellman%2C+Mr+N&rft.creator=Loftus%2C+Dr+J&rft.creator=Nanthakumar%2C+Dr+B&rft.creator=Razi%2C+Dr+K&rft.creator=Stewart%2C+Mr+J&rft.creator=Comazzi%2C+Dr+M&rft.creator=Vita%2C+Dr+A&rft.creator=Heffner%2C+Dr+T&rft.creator=Sherrington%2C+Dr+R&rft.subject=Neurogenetics&rft.description=OBJECTIVE%3A+Some+genome-wide+scans+and+association+studies+for+schizophrenia+susceptibility+genes+have+yielded+significant+positive+findings%2C+but+there+is+disagreement+between+studies+on+their+locations%2C+and+no+mutation+has+yet+been+found+in+any+gene.+Since+schizophrenia+is+a+complex+disorder%2C+a+study+with+sufficient+power+to+detect+a+locus+with+a+small+or+moderate+gene+effect+is+necessary.+METHOD%3A+In+a+genome-wide+scan+of+382+sibling+pairs+with+a+diagnosis+of+schizophrenia+or+schizoaffective+disorder%2C+396+highly+polymorphic+markers+spaced+approximately+10+centimorgans+apart+throughout+the+genome+were+genotyped+in+all+individuals.+Multipoint+nonparametric+linkage+analysis+was+performed+to+evaluate+regions+of+the+genome+demonstrating+increased+allele+sharing%2C+as+measured+by+a+lod+score.+RESULTS%3A+Two+regions+with+multipoint+maximum+lod+scores+suggesting+linkage+were+found.+The+highest+lod+scores+occurred+on+chromosome+10p15-p13+(peak+lod+score+of+3.60+at+marker+D10S189)+and+the+centromeric+region+of+chromosome+2+(peak+lod+score+of+2.99+at+marker+D2S139).+In+addition%2C+a+maximum+lod+score+of+2.00+was+observed+with+marker+D22S283+on+chromosome+22q12%2C+which+showed+evidence+of+an+imprinting+effect%2C+whereby+an+excess+sharing+of+maternal%2C+but+not+paternal%2C+alleles+was+present.+No+evidence+of+linkage+was+obtained+at+several+locations+identified+in+previous+studies%2C+including+chromosomes+1q%2C+4p%2C+5p-q%2C+6p%2C+8p%2C+13q%2C+15p%2C+and+18p.+CONCLUSIONS%3A+The+findings+of+this+large+genome-wide+scan+emphasize+the+weakness+and+fragility+of+linkage+reports+on+schizophrenia.+No+linkage+appears+to+be+consistently+replicable+across+large+studies.+Thus%2C+it+has+to+be+questioned+whether+the+genetic+contribution+to+this+disorder+is+detectable+by+these+strategies+and+the+possibility+raised+that+it+may+be+epigenetic%2C+i.e.%2C+related+to+gene+expression+rather+than+sequence+variation.+Nevertheless%2C+the+positive+findings+on+chromosome+2%2C+10%2C+and+22+should+be+pursued+further.+%0A&rft.date=2002&rft.type=Journal+(Paginated)&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.identifier=http%3A%2F%2Fcogprints.org%2F3880%2F1%2FAJP82002DeLisi.pdf&rft.identifier=++DeLisi%2C+Prof+LE+and+Shaw%2C+Dr+SH+and+Crow%2C+Prof+TJ+and+Shields%2C+Dr+G+and+Smith%2C+Ms+AB+and+Larach%2C+Dr+VW+and+Wellman%2C+Mr+N+and+Loftus%2C+Dr+J+and+Nanthakumar%2C+Dr+B+and+Razi%2C+Dr+K+and+Stewart%2C+Mr+J+and+Comazzi%2C+Dr+M+and+Vita%2C+Dr+A+and+Heffner%2C+Dr+T+and+Sherrington%2C+Dr+R++(2002)+A+Genome-Wide+Scan+for+Linkage+to+Chromosomal+Regions+in+382+Sibling+Pairs+with+Schizophrenia+or+Schizoaffective+Disorder.++%5BJournal+(Paginated)%5D+++++&rft.relation=http%3A%2F%2Fcogprints.org%2F3880%2F