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Haljas K, Amare AT, Alizadeh BZ, et al. Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. Psychosom Med. 2018;80(3):242-251doi: 10.1097/PSY.0000000000000555.
Haljas, K., Amare, A. T., Alizadeh, B. Z., Hsu, Y. H., Mosley, T., Newman, A., Murabito, J., Tiemeier, H., Tanaka, T., van Duijn, C., Ding, J., Llewellyn, D. J., Bennett, D. A., Terracciano, A., Launer, L., Ladwig, K. H., Cornelis, M. C., Teumer, A., Grabe, H., Kardia, S. L. R., Ware, E. B., Smith, J. A., Snieder, H., Eriksson, J. G., Groop, L., Räikkönen, K., & Lahti, J. (2018). Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. Psychosomatic medicine, 80(3), 242-251. https://doi.org/10.1097/PSY.0000000000000555
Haljas, Kadri, et al. "Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits." Psychosomatic medicine vol. 80,3 (2018): 242-251. doi: https://doi.org/10.1097/PSY.0000000000000555
Haljas K, Amare AT, Alizadeh BZ, Hsu YH, Mosley T, Newman A, Murabito J, Tiemeier H, Tanaka T, van Duijn C, Ding J, Llewellyn DJ, Bennett DA, Terracciano A, Launer L, Ladwig KH, Cornelis MC, Teumer A, Grabe H, Kardia SLR, Ware EB, Smith JA, Snieder H, Eriksson JG, Groop L, Räikkönen K, Lahti J. Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits. Psychosom Med. 2018 Apr;80(3):242-251. doi: 10.1097/PSY.0000000000000555. PMID: 29280852; PMCID: PMC6051528.
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Psychosom Med. 2018 Apr;80(3):242-251. doi: 10.1097/PSY.0000000000000555.

Bivariate Genome-Wide Association Study of Depressive Symptoms With Type 2 Diabetes and Quantitative Glycemic Traits.

Psychosomatic medicine

Kadri Haljas, Azmeraw T Amare, Behrooz Z Alizadeh, Yi-Hsiang Hsu, Thomas Mosley, Anne Newman, Joanne Murabito, Henning Tiemeier, Toshiko Tanaka, Cornelia van Duijn, Jingzhong Ding, David J Llewellyn, David A Bennett, Antonio Terracciano, Lenore Launer, Karl-Heinz Ladwig, Marylin C Cornelis, Alexander Teumer, Hans Grabe, Sharon L R Kardia, Erin B Ware, Jennifer A Smith, Harold Snieder, Johan G Eriksson, Leif Groop, Katri Räikkönen, Jari Lahti

Affiliations

  1. From the Departments of Psychology and Logopedics (Haljas, Räikkönen) and Psychology and Logopedics, Faculty of Medicine (Lahti), and Helsinki Collegium for Advanced Studies (Lahti), University of Helsinki, Helsinki, Finland; Department of Epidemiology (Amare, Alizadeh, Snieder), University of Groningen, University Medical Center Groningen, Groningen, the Netherlands; Harvard Medical School (Hsu), Boston, Massachusetts; Institute for Molecular Medicine Finland (FIMM) (Groop), Helsinki, Finland; Lund University Diabetes Centre (Groop), Lund University, Lund, Sweden; Department of General Practice and Primary Health Care (Eriksson), University of Helsinki and Helsinki University Hospital; Folkhälsan Research Center (Eriksson), Helsinki, Finland; Department of Medicine (Mosley), University of Mississippi Medical Center, Jackson, Mississippi; Department of Epidemiology, School of Public Health (Newman), University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Medicine, Section of General Internal Medicine (Murabito), Boston University School of Medicine, Boston; Boston University and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts (Murabito); Departments of Epidemiology and Psychiatry (Tiemeier), Erasmus University Medical Center, Rotterdam, the Netherlands; Translational Gerontology Branch (Tanaka), National Institute on Aging, Baltimore, Maryland; Genetic Epidemiology Unit, Department of Epidemiology (van Duijn), Erasmus University Medical Center, Rotterdam; Centre for Medical Systems Biology (van Duijn), Leiden, the Netherlands; Department of Internal Medicine, Division of Geriatrics (Ding), Wake Forest University, Winston-Salem, North Carolina; University of Exeter Medical School (Llewellyn), Exeter, UK; Rush Alzheimer's Disease Center (Bennett), Chicago, Illinois; Florida State University, College of Medicine (Terracciano), Tallahassee, Florida; Laboratory of Epidemiology and Population Sciences (Launer), National Institute on Aging, Bethesda, Maryland; Department of Psychiatry and Psychotherapy (Grabe), Helios Hospital Stralsund; Department of Psychiatry and Psychotherapy (Grabe) and Institute for Community Medicine (Teumer), University Medicine Greifswald; German Center for Neurodegenerative Diseases (Grabe), Site Rostock/Greifswald, Greifswald, Germany; Institute of Epidemiology II, Mental Health Research Unit, Helmholtz Zentrum München (Ladwig), German Research Center for Environmental Health, Neuherberg, Germany; Psychosomatic Medicine and Psychotherapy (Ladwig), Universitäts-Klinikum Rechts der Isar, Technische Universität München, Munich, Germany & German Center for Diabetes Research (DZD), München-Neuherberg, Germany; Department of Preventive Medicine (Cornelis), Northwestern University Feinberg School of Medicine, Chicago, Illinois; and Department of Epidemiology, School of Public Health (Kardia, Ware, Smith), and Survey Research Center, Institute for Social Research (Ware, Smith), University of Michigan, Ann Arbor, Michigan.

PMID: 29280852 PMCID: PMC6051528 DOI: 10.1097/PSY.0000000000000555

Abstract

OBJECTIVE: Shared genetic background may explain phenotypic associations between depression and Type 2 diabetes (T2D). We aimed to study, on a genome-wide level, if genetic correlation and pleiotropic loci exist between depressive symptoms and T2D or glycemic traits.

METHODS: We estimated single-nucleotide polymorphism (SNP)-based heritability and analyzed genetic correlation between depressive symptoms and T2D and glycemic traits with the linkage disequilibrium score regression by combining summary statistics of previously conducted meta-analyses for depressive symptoms by CHARGE consortium (N = 51,258), T2D by DIAGRAM consortium (N = 34,840 patients and 114,981 controls), fasting glucose, fasting insulin, and homeostatic model assessment of β-cell function and insulin resistance by MAGIC consortium (N = 58,074). Finally, we investigated pleiotropic loci using a bivariate genome-wide association study approach with summary statistics from genome-wide association study meta-analyses and reported loci with genome-wide significant bivariate association p value (p < 5 × 10). Biological annotation and function of significant pleiotropic SNPs were assessed in several databases.

RESULTS: The SNP-based heritability ranged from 0.04 to 0.10 in each individual trait. In the linkage disequilibrium score regression analyses, depressive symptoms showed no significant genetic correlation with T2D or glycemic traits (p > 0.37). However, we identified pleiotropic genetic variations for depressive symptoms and T2D (in the IGF2BP2, CDKAL1, CDKN2B-AS, and PLEKHA1 genes), and fasting glucose (in the MADD, CDKN2B-AS, PEX16, and MTNR1B genes).

CONCLUSIONS: We found no significant overall genetic correlations between depressive symptoms, T2D, or glycemic traits suggesting major differences in underlying biology of these traits. However, several potential pleiotropic loci were identified between depressive symptoms, T2D, and fasting glucose, suggesting that previously established phenotypic associations may be partly explained by genetic variation in these specific loci.

References

  1. Prim Care Companion J Clin Psychiatry. 2008;10(2):120-8 - PubMed
  2. J Clin Pathol. 2005 Aug;58(8):826-32 - PubMed
  3. Mol Psychiatry. 2006 Oct;11(10):929-33 - PubMed
  4. Hum Psychopharmacol. 2008 Oct;23(7):571-85 - PubMed
  5. J Infect Dis. 2008 Apr 15;197(8):1171-84 - PubMed
  6. Circ Cardiovasc Genet. 2014 Jun;7(3):374-382 - PubMed
  7. Am J Epidemiol. 2003 Sep 1;158(5):416-23 - PubMed
  8. Nat Genet. 2009 Jan;41(1):82-8 - PubMed
  9. Mol Psychiatry. 2013 Dec;18(12):1281-6 - PubMed
  10. Br J Psychiatry. 2010 May;196(5):365-71 - PubMed
  11. Sci Rep. 2017 Mar 13;7:38837 - PubMed
  12. Lancet. 2016 Apr 9;387(10027):1513-30 - PubMed
  13. Neuroscientist. 2013 Oct;19(5):479-94 - PubMed
  14. Psychol Med. 2004 Apr;34(3):471-9 - PubMed
  15. Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15506-11 - PubMed
  16. Mol Psychiatry. 2016 Jul;21(7):903-9 - PubMed
  17. Genes (Basel). 2015 Jun 23;6(2):372-84 - PubMed
  18. Psychosom Med. 2015 Jun;77(5):559-66 - PubMed
  19. Nat Genet. 2015 Mar;47(3):291-5 - PubMed
  20. Diabetes Care. 2004 Jun;27(6):1487-95 - PubMed
  21. Diabetes Care. 2011 Dec;34(12):2545-7 - PubMed
  22. Diabetologia. 2010 Dec;53(12):2480-6 - PubMed
  23. Nat Rev Genet. 2013 Jul;14(7):483-95 - PubMed
  24. Psychosom Med. 2016 Feb-Mar;78(2):233-41 - PubMed
  25. Psychiatry Res. 2011 Oct 30;189(3):472-4 - PubMed
  26. Psychosom Med. 2015 May;77(4):467-77 - PubMed
  27. Cell Metab. 2014 Mar 4;19(3):380-92 - PubMed
  28. J Clin Psychiatry. 2013 Apr;74(4):e287-92 - PubMed
  29. Can J Diabetes. 2015 Aug;39(4):266-72 - PubMed
  30. Nat Rev Genet. 2013 Feb;14(2):139-49 - PubMed
  31. J Psychiatry Neurosci. 2014 Jan;39(1):6-21 - PubMed
  32. Diabetologia. 2006 May;49(5):837-45 - PubMed
  33. J Clin Pathol. 2014 Dec;67(12):1078-83 - PubMed
  34. Nat Genet. 2010 Dec;42(12):1118-25 - PubMed
  35. Nat Genet. 2015 Nov;47(11):1236-41 - PubMed
  36. BMC Genomics. 2016 Jun 10;17:443 - PubMed
  37. Lancet Diabetes Endocrinol. 2015 Jun;3(6):461-471 - PubMed
  38. World J Biol Psychiatry. 2012 Dec;13(8):599-604 - PubMed
  39. J Biol Rhythms. 2011 Oct;26(5):423-33 - PubMed
  40. Trends Mol Med. 2004 Oct;10(10):476-80 - PubMed
  41. Nat Genet. 2009 Jan;41(1):47-55 - PubMed
  42. Nat Genet. 2010 Nov;42(11):985-90 - PubMed
  43. J Affect Disord. 2015 Jun 1;178:206-14 - PubMed
  44. Psychosom Med. 2015 Nov-Dec;77(9):982-92 - PubMed
  45. J Abnorm Psychol. 2005 Feb;114(1):96-110 - PubMed
  46. Psychol Methods. 2002 Mar;7(1):19-40 - PubMed
  47. Genes (Basel). 2015 Mar 12;6(1):87-123 - PubMed
  48. PLoS Med. 2013 Nov;10(11):e1001547 - PubMed
  49. Biol Psychiatry. 2013 Apr 1;73(7):667-78 - PubMed
  50. PLoS Genet. 2009 Dec;5(12):e1000792 - PubMed
  51. Psychosom Med. 2016 Feb-Mar;78(2):221-32 - PubMed
  52. Psychol Med. 2012 Nov;42(11):2275-85 - PubMed
  53. Am J Med Genet B Neuropsychiatr Genet. 2017 Apr;174(3):227-234 - PubMed
  54. J Affect Disord. 2004 Apr;79(1-3):71-9 - PubMed
  55. Parkinsonism Relat Disord. 2015 Dec;21(12):1435-40 - PubMed
  56. Nat Genet. 2012 Sep;44(9):981-90 - PubMed
  57. JAMA Psychiatry. 2014 Jun;71(6):657-64 - PubMed
  58. Nat Genet. 2010 Feb;42(2):105-16 - PubMed
  59. Psychoneuroendocrinology. 2016 Jul;69:123-32 - PubMed
  60. Clin Psychol Rev. 2011 Dec;31(8):1239-46 - PubMed

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