4.8 Article

Whole-genome association study of bipolar disorder

期刊

MOLECULAR PSYCHIATRY
卷 13, 期 6, 页码 558-569

出版社

NATURE PUBLISHING GROUP
DOI: 10.1038/sj.mp.4002151

关键词

genetic; schizophrenia; CACNA1C; MYO5B; TSPAN8; EGFR

资金

  1. EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT [R01HD060726] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH059548, R01MH059553, R01MH059571, R01MH059535, R01MH059545, R01MH059533, R01MH059586, R01MH059565, RC2MH089905, R01MH059534, R01MH067257, R01MH059588, R01MH062137, N01MH080001, R01MH059567, R01MH059566, R01MH060879, R01MH059556, R01MH061675, R01MH060068, R01MH067288, R01MH063420, Z01MH002810, R01MH060870, R01MH063445, R01MH059587] Funding Source: NIH RePORTER
  3. MRC [G0500791] Funding Source: UKRI
  4. Intramural NIH HHS [Z01 MH002810] Funding Source: Medline
  5. Medical Research Council [G9623693N, G0500791] Funding Source: Medline
  6. NHGRI NIH HHS [R01 HG005827] Funding Source: Medline
  7. NICHD NIH HHS [R01 HD060726] Funding Source: Medline
  8. NIMH NIH HHS [R01 MH59533, R01 MH062137, R01 MH059567, MH63420, R01 MH067288, MH059588, MH067288, R01 MH059588, R01 MH59567, N01MH80001, R01 MH059553, R01 MH063445, R01 MH061675, MH061675, R01 MH059556, MH60870, MH59586, MH59566, MH063445, R01 MH59545, R01 MH059535, RC2 MH089905, MH059571, U01 MH060879, R01 MH060879, MH59587, R01 MH060068, R01 MH059533, MH059565, R01 MH059587, R01 MH60068, R01 MH59553, R01 MH059586, R01 MH59535, R01 MH059565, R01 MH059571, R01 MH059534, MH062137, R01 MH060870, R01 MH059566, R01 MH059545, MH067257, R01 MH059548, R01 MH063420, R01 MH067257] Funding Source: Medline
  9. Wellcome Trust [066717] Funding Source: Medline

向作者/读者索取更多资源

We performed a genome-wide association scan in 1461 patients with bipolar (BP) 1 disorder, 2008 controls drawn from the Systematic Treatment Enhancement Program for Bipolar Disorder and the University College London sample collections with successful genotyping for 372 193 single nucleotide polymorphisms (SNPs). Our strongest single SNP results are found in myosin5B (MYO5B; P = 1.66 x 10(-7)) and tetraspanin-8 (TSPAN8; P = 6.11 x 10(-7)). Haplotype analysis further supported single SNP results highlighting MYO5B, TSPAN8 and the epidermal growth factor receptor (MYO5B; P = 2.04 x 10(-8), TSPAN8; P = 7.57 x 10(-7) and EGFR; P = 8.36 x 10(-8)). For replication, we genotyped 304 SNPs in family-based NIMH samples (n = 409 trios) and University of Edinburgh case-control samples (n = 365 cases, 351 controls) that did not provide independent replication after correction for multiple testing. A comparison of our strongest associations with the genome-wide scan of 1868 patients with BP disorder and 2938 controls who completed the scan as part of the Wellcome Trust Case-Control Consortium indicates concordant signals for SNPs within the voltage-dependent calcium channel, L-type, alpha 1C subunit (CACNA1C) gene. Given the heritability of BP disorder, the lack of agreement between studies emphasizes that susceptibility alleles are likely to be modest in effect size and require even larger samples for detection.

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