TY - JOUR
T1 - Genomewide linkage scan of 409 European-ancestry and African American families with schizophrenia
T2 - Suggestive evidence of linkage at 8p23.3-p21.2 and 11p13.1-q14.1 in the combined sample
AU - Suarez, Brian K.
AU - Duan, Jubao
AU - Sanders, Alan R.
AU - Hinrichs, Anthony L.
AU - Jin, Carol H.
AU - Hou, Cuiping
AU - Buccola, Nancy G.
AU - Hale, Nancy
AU - Weilbaecher, Ann N.
AU - Nertney, Deborah A.
AU - Olincy, Ann
AU - Green, Susan
AU - Schaffer, Arthur W.
AU - Smith, Christopher J.
AU - Hannah, Dominique E.
AU - Rice, John P.
AU - Cox, Nancy J.
AU - Martinez, Maria
AU - Mowry, Bryan J.
AU - Amin, Farooq
AU - Silverman, Jeremy M.
AU - Black, Donald W.
AU - Byerley, William F.
AU - Crowe, Raymond R.
AU - Freedman, Robert
AU - Cloninger, C. Robert
AU - Levinson, Douglas F.
AU - Gejman, Pablo V.
PY - 2006/2
Y1 - 2006/2
N2 - We report the clinical characteristics of a schizophrenia sample of 409 pedigrees-263 of European ancestry (EA) and 146 of African American ancestry (AA)-together with the results of a genome scan (with a simple tandem repeat polymorphism interval of 9 cM) and follow-up fine mapping. A family was required to have a proband with schizophrenia (SZ) and one or more siblings of the proband with SZ or schizoaffective disorder. Linkage analyses included 403 independent full-sibling affected sibling pairs (ASPs) (279 EA and 124 AA) and 100 all-possible half-sibling ASPs (15 EA and 85 AA). Nonparametric multipoint linkage analysis of all families detected two regions with suggestive evidence of linkage at 8p23.3-q12 and 11p11.2-q22.3 (empirical Z likelihood-ratio score [Z1r] threshold ≥2.65) and, in exploratory analyses, two other regions at 4p16.1-p15.32 in AA families and at 5p14.3-q11.2 in EA families. The most significant linkage peak was in chromosome 8p; its signal was mainly driven by the EA families. Z1r scores >2.0 in 8p were observed from 30.7 cM to 61.7 cM (Center for Inherited Disease Research map locations). The maximum evidence in the full sample was a multipoint Z1r of 3.25 (equivalent Kong-Cox LOD of 2.30) near D8S1771 (at 52 cM); there appeared to be two peaks, both telomeric to neuregulin 1 (NRG1). There is a paracentric inversion common in EA individuals within this region, the effect of which on the linkage evidence remains unknown in this and in other previously analyzed samples. Fine mapping of 8p did not significantly alter the significance or length of the peak. We also performed fine mapping of 4p16.3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z1r scores was observed for 5p14.1-q12.1, where the maximum Z 1r increased from 2.77 initially to 3.80 after fine mapping in the EA families.
AB - We report the clinical characteristics of a schizophrenia sample of 409 pedigrees-263 of European ancestry (EA) and 146 of African American ancestry (AA)-together with the results of a genome scan (with a simple tandem repeat polymorphism interval of 9 cM) and follow-up fine mapping. A family was required to have a proband with schizophrenia (SZ) and one or more siblings of the proband with SZ or schizoaffective disorder. Linkage analyses included 403 independent full-sibling affected sibling pairs (ASPs) (279 EA and 124 AA) and 100 all-possible half-sibling ASPs (15 EA and 85 AA). Nonparametric multipoint linkage analysis of all families detected two regions with suggestive evidence of linkage at 8p23.3-q12 and 11p11.2-q22.3 (empirical Z likelihood-ratio score [Z1r] threshold ≥2.65) and, in exploratory analyses, two other regions at 4p16.1-p15.32 in AA families and at 5p14.3-q11.2 in EA families. The most significant linkage peak was in chromosome 8p; its signal was mainly driven by the EA families. Z1r scores >2.0 in 8p were observed from 30.7 cM to 61.7 cM (Center for Inherited Disease Research map locations). The maximum evidence in the full sample was a multipoint Z1r of 3.25 (equivalent Kong-Cox LOD of 2.30) near D8S1771 (at 52 cM); there appeared to be two peaks, both telomeric to neuregulin 1 (NRG1). There is a paracentric inversion common in EA individuals within this region, the effect of which on the linkage evidence remains unknown in this and in other previously analyzed samples. Fine mapping of 8p did not significantly alter the significance or length of the peak. We also performed fine mapping of 4p16.3-p15.2, 5p15.2-q13.3, 10p15.3-p14, 10q25.3-q26.3, and 11p13-q23.3. The highest increase in Z1r scores was observed for 5p14.1-q12.1, where the maximum Z 1r increased from 2.77 initially to 3.80 after fine mapping in the EA families.
UR - http://www.scopus.com/inward/record.url?scp=31544444484&partnerID=8YFLogxK
U2 - 10.1086/500272
DO - 10.1086/500272
M3 - Article
C2 - 16400611
AN - SCOPUS:31544444484
SN - 0002-9297
VL - 78
SP - 315
EP - 333
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 2
ER -