The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome screen: first stage report

Bennett, P., Segurado, R., Jones, Ian Richard ORCID: https://orcid.org/0000-0001-5821-5889, Bort, S., McCandless, F., Lambert, D., Heron, J., Comerford, C., Middle, F., Corvin, A., Pelios, G., Kirov, George ORCID: https://orcid.org/0000-0002-3427-3950, Larsen, B., Mulcahy, T., Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, O'Connell, R., O'Mahony, E., Payne, A., Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862, Holmans, Peter Alan ORCID: https://orcid.org/0000-0003-0870-9412, Craddock, Nicholas John ORCID: https://orcid.org/0000-0003-2171-0610 and Gill, M. 2002. The Wellcome trust UK-Irish bipolar affective disorder sibling-pair genome screen: first stage report. Molecular Psychiatry 7 (2) , pp. 189-200. 10.1038/sj.mp.4000957

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Abstract

We have completed the first stage of a two-stage genome wide screen designed to identify chromosomal regions that may harbour susceptibility genes for bipolar affective disorder. The first stage screening sample included 509 subjects from 151 nuclear families recruited within the United Kingdom and Republic of Ireland. This sample contained 154 narrowly defined affected sibling pairs (DSM-IV BPI) and 258 broadly defined affected sibling pairs (DSM-IV BPI, SABP, BPII, BPNOS or MDD(R)), approximately two thirds of all families contained at least one other additional typed individual. All individuals were genotyped using 398 highly polymorphic microsatellite markers from Applied Biosystems's Linkage Mapping Set Version 2. The average inter-marker distance was 9.6 cM and the mean heterozygosity was 0.78. Analysis of these data using non-parametric linkage methods (MAPMAKER/SIBS) found no evidence for loci of major effect and no regions reached genome-wide significance for either suggestive or significant linkage. We identified 19 points across the genome where the MLS exceeded a value set for follow up in our second stage screen (MLS0.74 (equivalent to a nominal pointwise significance of 5%) under the narrowest diagnostic model). These points were on chromosomes 2, 3, 4, 6, 7, 9, 10, 12, 17, 18 & X. Some of these points overlapped with previous linkage reports both within bipolar affective disorder and other psychiatric illnesses. Under the narrowest diagnostic model, the single most significant multipoint linkage was on chromosome 18 at marker D18S452 (MLS=1.54). Overall the highest MLS was 1.70 on chromosome 2 at marker D2S125, under the broadest diagnostic model.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI) MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Subjects:	R Medicine > R Medicine (General)
Publisher:	Nature Publishing Group
ISSN:	1359-4184
Last Modified:	27 Oct 2022 08:24
URI:	https://orca.cardiff.ac.uk/id/eprint/62174

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