Combined Analysis from Eleven Linkage Studies of Bipolar Disorder Provides Strong Evidence of Susceptibility Loci on Chromosomes 6q and 8q
Open accessAbstract
Several independent studies and meta-analyses aimed at identifying genomic regions linked to bipolar disorder (BP) have failed to find clear and consistent evidence of linkage regions. Our hypothesis is that combining the original genotype data provides benefits of increased power and control over sources of heterogeneity that outweigh the difficulty and potential pitfalls of the implementation. We conducted a combined analysis using the original genotype data from 11 BP genomewide linkage scans comprising 5,179 individuals from 1,067 families. Heterogeneity among studies was minimized in our analyses by using uniform methods of analysis and a common, standardized marker map and was assessed using novel methods developed for meta-analysis of genome scans. To date, this collaboration is the largest and most comprehensive analysis of linkage samples involving a psychiatric disorder. We demonstrate that combining original genome-scan data is a powerful approach for the elucidation of linkage regions underlying complex disease. Our results establish genomewide significant linkage to BP on chromosomes 6q and 8q, which provides solid information to guide future gene-finding efforts that rely on fine-mapping and association approaches.
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Genetic linkage studies have been equivocal, yet modest associations have been reported between bipolar disorder and multiple genes of the molecular circadian clock.
“Genetic linkage studies have been equivocal115, yet modest associations have been reported between BD and multiple genes of the molecular circadian clock116,117.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [115]
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Self-citation
- Authors
- McQueen, M. B., Devlin, B., Faraone, S. V., Nimgaonkar, V. L., Sklar, P., Smoller, J. W., Abou Jamra, R., Albus, M., Bacanu, S.-A., Baron, M., Barrett, T. B., Berrettini, W., Blacker, D., Byerley, W., Cichon, S., Coryell, W., Craddock, N., Daly, M. J., DePaulo, J. R., Edenberg, H. J., Foroud, T., Gill, M., Gilliam, T. C., Hamshere, M., Jones, I., Jones, L., Juo, S.-H., Kelsoe, J. R., Lambert, D., Lange, C., Lerer, B., Liu, J., Maier, W., MacKinnon, J. D., McInnis, M. G., McMahon, F. J., Murphy, D. L., Nöthen, M. M., Nurnberger, J. I., Pato, C. N., Pato, M. T., Potash, J. B., Propping, P., Pulver, A. E., Rice, J. P., Rietschel, M., Scheftner, W., Schumacher, J., Segurado, R., Van Steen, K., Xie, W., Zandi, P. P., & Laird, N. M.
- Affiliations
- Harvard University (US)
- Corresponding author
- McQueen, Matthew B.
- ORCID
- McQueen, Matthew B.
- Devlin, B.
- Faraone, Stephen V.
- Nimgaonkar, Vishwajit L.
- Sklar, Pamela
- Smoller, Jordan W.
- Albus, Margot
- Bacanu, Silviu-Alin
- Barrett, Thomas B.
- Berrettini, Wade
- Blacker, Deborah
- Byerley, William
- Cichon, Sven
- Craddock, Nick
- Daly, Mark J.
- DePaulo, J. Raymond
- Edenberg, Howard J.
- Foroud, Tatiana
- Gill, Michael
- Hamshere, Marian
- Jones, Ian
- Jones, Lisa
- Juo, Suh-Hang
- Kelsoe, John R.
- Lange, Christoph
- Lerer, Bernard
- Liu, Jianjun
- Maier, Wolfgang
- McInnis, Melvin G.
- McMahon, Francis J.
- Nöthen, Markus M.
- Pato, Carlos N.
- Pato, Michele T.
- Potash, James B.
- Rice, John P.
- Rietschel, Marcella
- Schumacher, Johannes
- Segurado, Ricardo
- Zandi, Peter P.
- Laird, Nan M.
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2005-10
- Volume
- 77
- Issue
- 4
- Pages
- 582-595
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1275607
- OpenAlex
- W2165540187
- Cited by
- 245
- References
- 62
- Citations by year
- 2024: 1 · 2023: 2 · 2022: 1 · 2021: 1 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 8 · 2015: 5 · 2014: 11 · 2013: 14 · 2012: 19
- FWCI
- 19.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
- Lirias (submittedVersion)
- Open Repository and Bibliography (University of Liège) (submittedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (N01-HG-65403)
- National Institute of Mental Health (MH0667288, T32-MH017119, MH63420, R01-MH063445)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- bipolar disorder, genetic linkage, genetic susceptibility loci, chromosome 6q, chromosome 8q, study heterogeneity, psychiatric genetics, fine mapping
- MeSH terms
- Bipolar Disorder, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 8, Humans, Genetic Linkage, Genetic Heterogeneity, Genetic Predisposition to Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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