Journal Article


N Craddock
M Gill
P Holmans
I Jones
L Jones
C Lendon
G Kirov
M J Owen
N Norton
P Bennett
and 12 others



genetics siblings lod score genome human bipolar disorder chromosomes human pair 10 male chromosomes human pair 4 chromosomes human pair 18 genetic testing genetic markers chromosomes human pair 6 chromosomes human pair 9 humans chromosome mapping parents female pedigree

Stage 2 of the Wellcome Trust UK-Irish bipolar affective disorder sibling-pair genome screen: evidence for linkage on chromosomes 6q16-q21, 4q12-q21, 9p21, 10p14-p12 and 18q22. (2005)

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). Multipoint 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> or =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.
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Full list of authors on original publication

N Craddock, M Gill, P Holmans, I Jones, L Jones, C Lendon, G Kirov, M J Owen, N Norton, P Bennett and 12 others

Experts in our system

Michael Gill
Trinity College Dublin
Total Publications: 273
Peter Holmans
Trinity College Dublin
Total Publications: 9
Michael J. Owen
Trinity College Dublin
Total Publications: 20