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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.
Mol Psychiatry. 2005 Sep; 10(9):831-41.MP

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.

Authors+Show Affiliations

Department of Genetics, Trinity College Dublin, Dublin, Republic of Ireland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15940300

Citation

Lambert, D, et al. "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." Molecular Psychiatry, vol. 10, no. 9, 2005, pp. 831-41.
Lambert D, Middle F, Hamshere ML, et al. 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. Mol Psychiatry. 2005;10(9):831-41.
Lambert, D., Middle, F., Hamshere, M. L., Segurado, R., Raybould, R., Corvin, A., Green, E., O'Mahony, E., Nikolov, I., Mulcahy, T., Haque, S., Bort, S., Bennett, P., Norton, N., Owen, M. J., Kirov, G., Lendon, C., Jones, L., Jones, I., ... Craddock, N. (2005). 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. Molecular Psychiatry, 10(9), 831-41.
Lambert D, et al. 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. Mol Psychiatry. 2005;10(9):831-41. PubMed PMID: 15940300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Lambert,D, AU - Middle,F, AU - Hamshere,M L, AU - Segurado,R, AU - Raybould,R, AU - Corvin,A, AU - Green,E, AU - O'Mahony,E, AU - Nikolov,I, AU - Mulcahy,T, AU - Haque,S, AU - Bort,S, AU - Bennett,P, AU - Norton,N, AU - Owen,M J, AU - Kirov,G, AU - Lendon,C, AU - Jones,L, AU - Jones,I, AU - Holmans,P, AU - Gill,M, AU - Craddock,N, PY - 2005/6/9/pubmed PY - 2005/11/9/medline PY - 2005/6/9/entrez SP - 831 EP - 41 JF - Molecular psychiatry JO - Mol. Psychiatry VL - 10 IS - 9 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). 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. SN - 1359-4184 UR - https://www.unboundmedicine.com/medline/citation/15940300/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_ L2 - http://dx.doi.org/10.1038/sj.mp.4001684 DB - PRIME DP - Unbound Medicine ER -