Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen provides evidence for suggestive linkage on chromosomes 6q16-q21 and 4q12-q21

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Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen provides evidence for suggestive linkage on chromosomes 6q16-q21 and 4q12-q21. / Lambert, D; Middle, Fiona; Hamshere, ML; Segurado, R; Raybould, R; Corvin, A; Green, Elaine; O'Mahony, E; Nikolov, I; Mulcahy, T; Haque, Mohammad; Bort, S; Bennett, P; Norton, N; Owen, MJ; Kirov, G; Lendon, Corinne; Jones, Lisa; Jones, Ian; Holmans, P; Gill, M; Craddock, Nicholas.

In: Molecular Psychiatry, Vol. 10, No. 9, 17.05.2005, p. 831-841.

Research output: Contribution to journalArticle

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Lambert, D, Middle, F, Hamshere, ML, Segurado, R, Raybould, R, Corvin, A, Green, E, O'Mahony, E, Nikolov, I, Mulcahy, T, Haque, M, Bort, S, Bennett, P, Norton, N, Owen, MJ, Kirov, G, Lendon, C, Jones, L, Jones, I, Holmans, P, Gill, M & Craddock, N 2005, 'Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen provides evidence for suggestive linkage on chromosomes 6q16-q21 and 4q12-q21', Molecular Psychiatry, vol. 10, no. 9, pp. 831-841. https://doi.org/10.1038/sj.mp.4001684

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Author

Lambert, D ; Middle, Fiona ; Hamshere, ML ; Segurado, R ; Raybould, R ; Corvin, A ; Green, Elaine ; O'Mahony, E ; Nikolov, I ; Mulcahy, T ; Haque, Mohammad ; Bort, S ; Bennett, P ; Norton, N ; Owen, MJ ; Kirov, G ; Lendon, Corinne ; Jones, Lisa ; Jones, Ian ; Holmans, P ; Gill, M ; Craddock, Nicholas. / Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen provides evidence for suggestive linkage on chromosomes 6q16-q21 and 4q12-q21. In: Molecular Psychiatry. 2005 ; Vol. 10, No. 9. pp. 831-841.

Bibtex

@article{0bf5969af86943b6b8518d40f53535e7,
title = "Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen provides evidence for suggestive linkage on chromosomes 6q16-q21 and 4q12-q21",
abstract = "Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD 3.30) and D10S197 (LOD 3.18). Multi-point analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS 2.61) and 4q12-q21 (MLS 2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS >= 1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22.",
keywords = "genetics, linkage, microsatellite repeats, manic-depressive, LOD score, genome scan",
author = "D Lambert and Fiona Middle and ML Hamshere and R Segurado and R Raybould and A Corvin and Elaine Green and E O'Mahony and I Nikolov and T Mulcahy and Mohammad Haque and S Bort and P Bennett and N Norton and MJ Owen and G Kirov and Corinne Lendon and Lisa Jones and Ian Jones and P Holmans and M Gill and Nicholas Craddock",
year = "2005",
month = may
day = "17",
doi = "10.1038/sj.mp.4001684",
language = "English",
volume = "10",
pages = "831--841",
journal = "Molecular Psychiatry",
issn = "1359-4184",
publisher = "Nature Publishing Group",
number = "9",

}

RIS

TY - JOUR

T1 - Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen provides evidence for suggestive linkage on chromosomes 6q16-q21 and 4q12-q21

AU - Lambert, D

AU - Middle, Fiona

AU - Hamshere, ML

AU - Segurado, R

AU - Raybould, R

AU - Corvin, A

AU - Green, Elaine

AU - O'Mahony, E

AU - Nikolov, I

AU - Mulcahy, T

AU - Haque, Mohammad

AU - Bort, S

AU - Bennett, P

AU - Norton, N

AU - Owen, MJ

AU - Kirov, G

AU - Lendon, Corinne

AU - Jones, Lisa

AU - Jones, Ian

AU - Holmans, P

AU - Gill, M

AU - Craddock, Nicholas

PY - 2005/5/17

Y1 - 2005/5/17

N2 - Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD 3.30) and D10S197 (LOD 3.18). Multi-point analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS 2.61) and 4q12-q21 (MLS 2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS >= 1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22.

AB - Bipolar affective disorder (BPAD) is a common psychiatric disorder with complex genetic aetiology. We have undertaken a genome-wide scan in one of the largest samples of bipolar affected sibling pairs (ASPs) using a two-stage approach combining sample splitting and marker grid tightening. In this second stage analysis, we have examined 17 regions that achieved a nominally significant maximum likelihood LOD score (MLS) threshold of 0.74 (or 1.18 for the X-chromosome) in stage one. The second stage has added 135 ASP families to bring the total stage 2 sample to 395 ASPs. In total, 494 microsatellite markers have been used to screen the human genome at a density of 10 cM in the first stage sample (260 ASPs) and 5 cM in the second stage. Under the broad diagnostic model, two markers gave LOD scores exceeding 3 with two-point analysis: D4S392 (LOD 3.30) and D10S197 (LOD 3.18). Multi-point analysis demonstrated suggestive evidence of linkage between BPAD and chromosomal regions 6q16-q21 (MLS 2.61) and 4q12-q21 (MLS 2.38). 6q16-q21 is of particular interest because our data, together with those from two recent genome scans, make this the best supported linkage region in BPAD. Further, our data show evidence of a gender effect at this locus with increased sharing predominantly within the male-male pairs. Our scan also provides support for linkage (MLS >= 1.5) at several other regions that have been implicated in meta-analyses of bipolar disorder and/or schizophrenia including 9p21, 10p14-p12 and 18q22.

KW - genetics

KW - linkage

KW - microsatellite repeats

KW - manic-depressive

KW - LOD score

KW - genome scan

UR - http://www.scopus.com/inward/record.url?scp=25444446614&partnerID=8YFLogxK

U2 - 10.1038/sj.mp.4001684

DO - 10.1038/sj.mp.4001684

M3 - Article

C2 - 15940300

VL - 10

SP - 831

EP - 841

JO - Molecular Psychiatry

JF - Molecular Psychiatry

SN - 1359-4184

IS - 9

ER -