Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study

Dieter B. Wildenauer; Sibylle G. Schwab; Margot Albus; Joachim Hallmayer; Bernard Lerer; Wolfgang Maier; Douglas Blackwood; Walter Muir; David St Clair; Stewart Morris; Hans W. Moises; Liu Yang; Helgi Kristbjarnarson; Tomas Helgason; Claudia Wiese; David A. Collier; Peter Holmans; Jo Daniels; Mark Rees; Philip Asherson; Queta Roberts; Alastair Cardno; Maria J. Arranz; Homero Vallada; David Ball; Hiroshi Kunugi; Robin M. Murray; John F. Powell; Sin Nanko; Pak Sham; Mike Gill; Peter McGuffin; Michael J. Owen; Ann E. Pulver; Stylianos E. Antonarakis; Robert Babb; Jean Louis Blouin; Nicola DeMarchi; Beth Dombroski; David Housman; Maria Karayiorgou; Jurg Ott; Laura Kasch; Haig Kazazian; Virginia K. Lasseter; Erika Loetscher; Hermann Luebbert; Gerald Nestadt; Carl Ton; Paula S. Wolyniec; Claudine Laurent; Michel de Chaldee; Florence Thibaut; Maurice Jay; Daniele Samolyk; Michel Petit; Dominique Campion; Jacques Mallet; Richard E. Straub; Charles J. MacLean; Stephen M. Easter; F. Anthony O'Neill; Dermot Walsh; Kenneth S. Kendler; Pablo V. Gejman; Qiuhe Cao; Elliot Gershon; Judith Badner; Ethiopia Beshah; Jing Zhang; Brien P. Riley; Swarnageetha Rajagopalan; Mpala Mogudi-Carter; Trefor Jenkins; Robert Williamson; Lynn E. DeLisi; Chad Garner; Mary Kelly; Carrie LeDuc; Lon Cardon; Jay Lichter; Tim Harris; Josephine Loftus; Gail Shields; Margarite Comasi; Antonio Vita; Angela Smith; Jay Dann; Geoff Joslyn; Hugh Gurling; Gursharan Kalsi; Jon Brynjolfsson; David Curtis; Thordur Sigmundsson; Robert Butler; Tim Read; Patrice Murphy; Andrew Chih Hui Chen; Hannes Petursson; Bill Byerley; Mark Hoff; John Holik; Hilary Coon; Douglas F. Levinson; Derek J. Nancarrow; Raymond R. Crowe; Nancy Andreasen; Jeremy M. Silverman; Richard C. Mohs; Larry J. Siever; Jean Endicott; Lawrence Sharpe; Marilyn K. Walters; David P. Lennon; Nicholas K. Hayward; Lodewijk A. Sandkuijl; Bryan J. Mowry; Harald N. Aschauer; Kurt Meszaros; Elisabeth Lenzinger; Karoline Fuchs; Liu Yang; Angela M. Heiden; Hans W. Moises; Leonid Kruglyak; Mark J. Daly; Tara C. Matise

doi:10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P

Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study

Dieter B. Wildenauer, Sibylle G. Schwab, Margot Albus, Joachim Hallmayer, Bernard Lerer, Wolfgang Maier, Douglas Blackwood, Walter Muir, David St Clair, Stewart Morris, Hans W. Moises, Liu Yang, Helgi Kristbjarnarson, Tomas Helgason, Claudia Wiese, David A. Collier, Peter Holmans, Jo Daniels, Mark Rees, Philip AshersonQueta Roberts, Alastair Cardno, Maria J. Arranz, Homero Vallada, David Ball, Hiroshi Kunugi, Robin M. Murray, John F. Powell, Sin Nanko, Pak Sham, Mike Gill, Peter McGuffin, Michael J. Owen, Ann E. Pulver, Stylianos E. Antonarakis, Robert Babb, Jean Louis Blouin, Nicola DeMarchi, Beth Dombroski, David Housman, Maria Karayiorgou, Jurg Ott, Laura Kasch, Haig Kazazian, Virginia K. Lasseter, Erika Loetscher, Hermann Luebbert, Gerald Nestadt, Carl Ton, Paula S. Wolyniec, Claudine Laurent, Michel de Chaldee, Florence Thibaut, Maurice Jay, Daniele Samolyk, Michel Petit, Dominique Campion, Jacques Mallet, Richard E. Straub, Charles J. MacLean, Stephen M. Easter, F. Anthony O'Neill, Dermot Walsh, Kenneth S. Kendler, Pablo V. Gejman, Qiuhe Cao, Elliot Gershon, Judith Badner, Ethiopia Beshah, Jing Zhang, Brien P. Riley, Swarnageetha Rajagopalan, Mpala Mogudi-Carter, Trefor Jenkins, Robert Williamson, Lynn E. DeLisi, Chad Garner, Mary Kelly, Carrie LeDuc, Lon Cardon, Jay Lichter, Tim Harris, Josephine Loftus, Gail Shields, Margarite Comasi, Antonio Vita, Angela Smith, Jay Dann, Geoff Joslyn, Hugh Gurling, Gursharan Kalsi, Jon Brynjolfsson, David Curtis, Thordur Sigmundsson, Robert Butler, Tim Read, Patrice Murphy, Andrew Chih Hui Chen, Hannes Petursson, Bill Byerley, Mark Hoff, John Holik, Hilary Coon, Douglas F. Levinson, Derek J. Nancarrow, Raymond R. Crowe, Nancy Andreasen, Jeremy M. Silverman, Richard C. Mohs, Larry J. Siever, Jean Endicott, Lawrence Sharpe, Marilyn K. Walters, David P. Lennon, Nicholas K. Hayward, Lodewijk A. Sandkuijl, Bryan J. Mowry, Harald N. Aschauer, Kurt Meszaros, Elisabeth Lenzinger, Karoline Fuchs, Liu Yang, Angela M. Heiden, Hans W. Moises, Leonid Kruglyak, Mark J. Daly, Tara C. Matise

School of Medicine

Research output: Contribution to journal › Article › peer-review

181 Scopus citations

Abstract

In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = .001) and 2.68 (Combined sample, p=.0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p=.0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.

Original language	English (US)
Pages (from-to)	580-594
Number of pages	15
Journal	American journal of medical genetics
Volume	67
Issue number	6
DOIs	https://doi.org/10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P
State	Published - 1996

Keywords

Collaboration
Genetic linkage
Genotype levinson
Polymorphism
Schizophrenia

ASJC Scopus subject areas

Genetics(clinical)

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10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P

Cite this

Wildenauer, D. B., Schwab, S. G., Albus, M., Hallmayer, J., Lerer, B., Maier, W., Blackwood, D., Muir, W., St Clair, D., Morris, S., Moises, H. W., Yang, L., Kristbjarnarson, H., Helgason, T., Wiese, C., Collier, D. A., Holmans, P., Daniels, J., Rees, M., ... Matise, T. C. (1996). Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study. American journal of medical genetics, 67(6), 580-594. https://doi.org/10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P

Wildenauer, DB, Schwab, SG, Albus, M, Hallmayer, J, Lerer, B, Maier, W, Blackwood, D, Muir, W, St Clair, D, Morris, S, Moises, HW, Yang, L, Kristbjarnarson, H, Helgason, T, Wiese, C, Collier, DA, Holmans, P, Daniels, J, Rees, M, Asherson, P, Roberts, Q, Cardno, A, Arranz, MJ, Vallada, H, Ball, D, Kunugi, H, Murray, RM, Powell, JF, Nanko, S, Sham, P, Gill, M, McGuffin, P, Owen, MJ, Pulver, AE, Antonarakis, SE, Babb, R, Blouin, JL, DeMarchi, N, Dombroski, B, Housman, D, Karayiorgou, M, Ott, J, Kasch, L, Kazazian, H, Lasseter, VK, Loetscher, E, Luebbert, H, Nestadt, G, Ton, C, Wolyniec, PS, Laurent, C, de Chaldee, M, Thibaut, F, Jay, M, Samolyk, D, Petit, M, Campion, D, Mallet, J, Straub, RE, MacLean, CJ, Easter, SM, O'Neill, FA, Walsh, D, Kendler, KS, Gejman, PV, Cao, Q, Gershon, E, Badner, J, Beshah, E, Zhang, J, Riley, BP, Rajagopalan, S, Mogudi-Carter, M, Jenkins, T, Williamson, R, DeLisi, LE, Garner, C, Kelly, M, LeDuc, C, Cardon, L, Lichter, J, Harris, T, Loftus, J, Shields, G, Comasi, M, Vita, A, Smith, A, Dann, J, Joslyn, G, Gurling, H, Kalsi, G, Brynjolfsson, J, Curtis, D, Sigmundsson, T, Butler, R, Read, T, Murphy, P, Chen, ACH, Petursson, H, Byerley, B, Hoff, M, Holik, J, Coon, H, Levinson, DF, Nancarrow, DJ, Crowe, RR, Andreasen, N, Silverman, JM, Mohs, RC, Siever, LJ, Endicott, J, Sharpe, L, Walters, MK, Lennon, DP, Hayward, NK, Sandkuijl, LA, Mowry, BJ, Aschauer, HN, Meszaros, K, Lenzinger, E, Fuchs, K, Yang, L, Heiden, AM, Moises, HW, Kruglyak, L, Daly, MJ & Matise, TC 1996, 'Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study', American journal of medical genetics, vol. 67, no. 6, pp. 580-594. https://doi.org/10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P

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title = "Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study",

abstract = "In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = .001) and 2.68 (Combined sample, p=.0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p=.0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.",

keywords = "Collaboration, Genetic linkage, Genotype levinson, Polymorphism, Schizophrenia",

author = "Wildenauer, {Dieter B.} and Schwab, {Sibylle G.} and Margot Albus and Joachim Hallmayer and Bernard Lerer and Wolfgang Maier and Douglas Blackwood and Walter Muir and {St Clair}, David and Stewart Morris and Moises, {Hans W.} and Liu Yang and Helgi Kristbjarnarson and Tomas Helgason and Claudia Wiese and Collier, {David A.} and Peter Holmans and Jo Daniels and Mark Rees and Philip Asherson and Queta Roberts and Alastair Cardno and Arranz, {Maria J.} and Homero Vallada and David Ball and Hiroshi Kunugi and Murray, {Robin M.} and Powell, {John F.} and Sin Nanko and Pak Sham and Mike Gill and Peter McGuffin and Owen, {Michael J.} and Pulver, {Ann E.} and Antonarakis, {Stylianos E.} and Robert Babb and Blouin, {Jean Louis} and Nicola DeMarchi and Beth Dombroski and David Housman and Maria Karayiorgou and Jurg Ott and Laura Kasch and Haig Kazazian and Lasseter, {Virginia K.} and Erika Loetscher and Hermann Luebbert and Gerald Nestadt and Carl Ton and Wolyniec, {Paula S.} and Claudine Laurent and {de Chaldee}, Michel and Florence Thibaut and Maurice Jay and Daniele Samolyk and Michel Petit and Dominique Campion and Jacques Mallet and Straub, {Richard E.} and MacLean, {Charles J.} and Easter, {Stephen M.} and O'Neill, {F. Anthony} and Dermot Walsh and Kendler, {Kenneth S.} and Gejman, {Pablo V.} and Qiuhe Cao and Elliot Gershon and Judith Badner and Ethiopia Beshah and Jing Zhang and Riley, {Brien P.} and Swarnageetha Rajagopalan and Mpala Mogudi-Carter and Trefor Jenkins and Robert Williamson and DeLisi, {Lynn E.} and Chad Garner and Mary Kelly and Carrie LeDuc and Lon Cardon and Jay Lichter and Tim Harris and Josephine Loftus and Gail Shields and Margarite Comasi and Antonio Vita and Angela Smith and Jay Dann and Geoff Joslyn and Hugh Gurling and Gursharan Kalsi and Jon Brynjolfsson and David Curtis and Thordur Sigmundsson and Robert Butler and Tim Read and Patrice Murphy and Chen, {Andrew Chih Hui} and Hannes Petursson and Bill Byerley and Mark Hoff and John Holik and Hilary Coon and Levinson, {Douglas F.} and Nancarrow, {Derek J.} and Crowe, {Raymond R.} and Nancy Andreasen and Silverman, {Jeremy M.} and Mohs, {Richard C.} and Siever, {Larry J.} and Jean Endicott and Lawrence Sharpe and Walters, {Marilyn K.} and Lennon, {David P.} and Hayward, {Nicholas K.} and Sandkuijl, {Lodewijk A.} and Mowry, {Bryan J.} and Aschauer, {Harald N.} and Kurt Meszaros and Elisabeth Lenzinger and Karoline Fuchs and Liu Yang and Heiden, {Angela M.} and Moises, {Hans W.} and Leonid Kruglyak and Daly, {Mark J.} and Matise, {Tara C.}",

year = "1996",

doi = "10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P",

language = "English (US)",

volume = "67",

pages = "580--594",

journal = "American journal of medical genetics",

issn = "0148-7299",

publisher = "Wiley-Liss Inc.",

number = "6",

}

TY - JOUR

T1 - Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8

T2 - A Multicenter Study

AU - Wildenauer, Dieter B.

AU - Schwab, Sibylle G.

AU - Albus, Margot

AU - Hallmayer, Joachim

AU - Lerer, Bernard

AU - Maier, Wolfgang

AU - Blackwood, Douglas

AU - Muir, Walter

AU - St Clair, David

AU - Morris, Stewart

AU - Moises, Hans W.

AU - Yang, Liu

AU - Kristbjarnarson, Helgi

AU - Helgason, Tomas

AU - Wiese, Claudia

AU - Collier, David A.

AU - Holmans, Peter

AU - Daniels, Jo

AU - Rees, Mark

AU - Asherson, Philip

AU - Roberts, Queta

AU - Cardno, Alastair

AU - Arranz, Maria J.

AU - Vallada, Homero

AU - Ball, David

AU - Kunugi, Hiroshi

AU - Murray, Robin M.

AU - Powell, John F.

AU - Nanko, Sin

AU - Sham, Pak

AU - Gill, Mike

AU - McGuffin, Peter

AU - Owen, Michael J.

AU - Pulver, Ann E.

AU - Antonarakis, Stylianos E.

AU - Babb, Robert

AU - Blouin, Jean Louis

AU - DeMarchi, Nicola

AU - Dombroski, Beth

AU - Housman, David

AU - Karayiorgou, Maria

AU - Ott, Jurg

AU - Kasch, Laura

AU - Kazazian, Haig

AU - Lasseter, Virginia K.

AU - Loetscher, Erika

AU - Luebbert, Hermann

AU - Nestadt, Gerald

AU - Ton, Carl

AU - Wolyniec, Paula S.

AU - Laurent, Claudine

AU - de Chaldee, Michel

AU - Thibaut, Florence

AU - Jay, Maurice

AU - Samolyk, Daniele

AU - Petit, Michel

AU - Campion, Dominique

AU - Mallet, Jacques

AU - Straub, Richard E.

AU - MacLean, Charles J.

AU - Easter, Stephen M.

AU - O'Neill, F. Anthony

AU - Walsh, Dermot

AU - Kendler, Kenneth S.

AU - Gejman, Pablo V.

AU - Cao, Qiuhe

AU - Gershon, Elliot

AU - Badner, Judith

AU - Beshah, Ethiopia

AU - Zhang, Jing

AU - Riley, Brien P.

AU - Rajagopalan, Swarnageetha

AU - Mogudi-Carter, Mpala

AU - Jenkins, Trefor

AU - Williamson, Robert

AU - DeLisi, Lynn E.

AU - Garner, Chad

AU - Kelly, Mary

AU - LeDuc, Carrie

AU - Cardon, Lon

AU - Lichter, Jay

AU - Harris, Tim

AU - Loftus, Josephine

AU - Shields, Gail

AU - Comasi, Margarite

AU - Vita, Antonio

AU - Smith, Angela

AU - Dann, Jay

AU - Joslyn, Geoff

AU - Gurling, Hugh

AU - Kalsi, Gursharan

AU - Brynjolfsson, Jon

AU - Curtis, David

AU - Sigmundsson, Thordur

AU - Butler, Robert

AU - Read, Tim

AU - Murphy, Patrice

AU - Chen, Andrew Chih Hui

AU - Petursson, Hannes

AU - Byerley, Bill

AU - Hoff, Mark

AU - Holik, John

AU - Coon, Hilary

AU - Levinson, Douglas F.

AU - Nancarrow, Derek J.

AU - Crowe, Raymond R.

AU - Andreasen, Nancy

AU - Silverman, Jeremy M.

AU - Mohs, Richard C.

AU - Siever, Larry J.

AU - Endicott, Jean

AU - Sharpe, Lawrence

AU - Walters, Marilyn K.

AU - Lennon, David P.

AU - Hayward, Nicholas K.

AU - Sandkuijl, Lodewijk A.

AU - Mowry, Bryan J.

AU - Aschauer, Harald N.

AU - Meszaros, Kurt

AU - Lenzinger, Elisabeth

AU - Fuchs, Karoline

AU - Yang, Liu

AU - Heiden, Angela M.

AU - Moises, Hans W.

AU - Kruglyak, Leonid

AU - Daly, Mark J.

AU - Matise, Tara C.

PY - 1996

Y1 - 1996

N2 - In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = .001) and 2.68 (Combined sample, p=.0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p=.0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.

AB - In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = .001) and 2.68 (Combined sample, p=.0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p=.0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.

KW - Collaboration

KW - Genetic linkage

KW - Genotype levinson

KW - Polymorphism

KW - Schizophrenia

UR - http://www.scopus.com/inward/record.url?scp=0029845435&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029845435&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P

DO - 10.1002/(SICI)1096-8628(19961122)67:6<580::AID-AJMG11>3.0.CO;2-P

M3 - Article

C2 - 8950417

AN - SCOPUS:0029845435

SN - 0148-7299

VL - 67

SP - 580

EP - 594

JO - American journal of medical genetics

JF - American journal of medical genetics

IS - 6

ER -

Additional Support for Schizophrenia Linkage on Chromosomes 6 and 8: A Multicenter Study

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