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Genome-wide association study of bipolar disorder in European American and African American individuals
Open accessAbstract
To identify bipolar disorder (BD) genetic susceptibility factors, we conducted two genome-wide association (GWA) studies: one involving a sample of individuals of European ancestry (EA; n=1001 cases; n=1033 controls), and one involving a sample of individuals of African ancestry (AA; n=345 cases; n=670 controls). For the EA sample, single-nucleotide polymorphisms (SNPs) with the strongest statistical evidence for association included rs5907577 in an intergenic region at Xq27.1 (P=1.6 x 10(-6)) and rs10193871 in NAP5 at 2q21.2 (P=9.8 x 10(-6)). For the AA sample, SNPs with the strongest statistical evidence for association included rs2111504 in DPY19L3 at 19q13.11 (P=1.5 x 10(-6)) and rs2769605 in NTRK2 at 9q21.33 (P=4.5 x 10(-5)). We also investigated whether we could provide support for three regions previously associated with BD, and we showed that the ANK3 region replicates in our sample, along with some support for C15Orf53; other evidence implicates BD candidate genes such as SLITRK2. We also tested the hypothesis that BD susceptibility variants exhibit genetic background-dependent effects. SNPs with the strongest statistical evidence for genetic background effects included rs11208285 in ROR1 at 1p31.3 (P=1.4 x 10(-6)), rs4657247 in RGS5 at 1q23.3 (P=4.1 x 10(-6)), and rs7078071 in BTBD16 at 10q26.13 (P=4.5 x 10(-6)). This study is the first to conduct GWA of BD in individuals of AA and suggests that genetic variations that contribute to BD may vary as a function of ancestry.
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“We extended our analysis of pathways identified in this study (Table 4 and Table 5, and S7) to rare CNVs from large case-controls studies of SCZ and BD. These included rare CNVs from 8,290 SCZ cases and 7,431 controls from Vacic et al. (2011), a combined sample of three studies from our group, MGS (Levinson et al., 2011), and the International Schizophrenia Consortium (International Schizophrenia”
From High frequencies of de novo CNVs in bipolar disorder and schizophrenia (2011) · cites this paper as Smith et al., 2009
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Genome-wide association study identifies 30 loci associated with bipolar disorder
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Self-citationMullins, N., Forstner, A. J., O’Connell, K. S., Coombes, B., Coleman, J. R. I., Qiao, Z., Als, T. D., Bigdeli, T. B., Børte, S., Bryois, J., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00857-4 · Cited by 1,517
Self-citationPsychiatric GWAS Consortium Bipolar Disorder Working Group, Sklar, P., Ripke, S., Scott, L. J., Andreassen, O. A., Cichon, S., Craddock, N., Edenberg, H. J., Nurnberger, J. I., Rietschel, M., et al. (2011) · Nature Genetics · doi:10.1038/ng.943 · Cited by 1,344
Self-citationCraddock, N. J., & Sklar, P. B. (2013) · The Lancet · doi:10.1016/s0140-6736(13)60855-7 · Cited by 684
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Metadata
- Authors
- Smith, E. N., Bloss, C. S., Badner, J. A., Barrett, T., Belmonte, P. L., Berrettini, W., Byerley, W., Coryell, W., Craig, D., Edenberg, H. J., Eskin, E., Foroud, T., Gershon, E., Greenwood, T. A., Hipolito, M., Koller, D. L., Lawson, W. B., Liu, C., Lohoff, F., McInnis, M. G., McMahon, F. J., Mirel, D. B., Murray, S. S., Nievergelt, C., Nurnberger, J., Nwulia, E. A., Paschall, J., Potash, J. B., Rice, J., Schulze, T. G., Scheftner, W., Panganiban, C., Zaitlen, N., Zandi, P. P., Zöllner, S., Schork, N. J., & Kelsoe, J. R.
- Affiliations
- Scripps Health (US)
- University of Chicago (US)
- Portland VA Medical Center (US)
- Johns Hopkins University (US)
- University of Pennsylvania (US)
- University of California, San Francisco (US)
- University of Iowa (US)
- Translational Genomics Research Institute (US)
- Indiana University Indianapolis (US)
- University of California, Los Angeles (US)
- University of California San Diego (US)
- Howard University (US)
- Indiana University School of Medicine (US)
- University of Michigan (US)
- National Institutes of Health (US)
- Broad Institute (US)
- Scripps Research Institute (US)
- Washington University in St. Louis (US)
- Rush University (US)
- Corresponding author
- Schork, N J
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2009-06-02
- Volume
- 14
- Issue
- 8
- Pages
- 755-763
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- PMC
- PMC3035981
- OpenAlex
- W2136702573
- Cited by
- 363
- References
- 51
- Citations by year
- 2026: 1 · 2025: 10 · 2024: 5 · 2023: 10 · 2022: 8 · 2021: 14 · 2020: 19 · 2019: 15 · 2018: 16 · 2017: 21 · 2016: 17 · 2015: 22 · 2014: 30 · 2013: 37 · 2012: 52
- FWCI
- 27.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institutes of Health (5u01mh046280-08, 5u01mh046274-08)
- University of California, San Diego
- National Heart, Lung, and Blood Institute (K25HL080079)
- National Institute of Mental Health (R01MH059553, Z01MH002810, MH081804, R01MH078151, R01MH059545, R01MH059534, R01MH059533, U01MH046282, R01MH059567, R01MH059556, MH078151, R01MH059535, R01MH094483, U01 MH 46280, R01MH081804, K01MH072866, R01MH059548, R01MH060068, K08MH080372, MH059567, U01 MH 46274)
- National Human Genome Research Institute
- National Center for Research Resources (1U54RR025204-01, UL1RR025774)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Keywords
- bipolar disorder, genetic susceptibility, single nucleotide polymorphisms, African American ancestry, NTRK2, ANK3, ROR1, RGS5, candidate genes
- MeSH terms
- Adolescent, Adult, Bipolar Disorder, Black or African American, Female, Haplotypes, Humans, Male, Middle Aged, Reference Values, Cohort Studies, Genome, Human, Case-Control Studies, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study, Young Adult
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