Association of body mass index-related single nucleotide polymorphisms with psychiatric disease and memory performance in a Japanese population

Midori Ninomiya-Baba; Junko Matsuo; Daimei Sasayama; Hiroaki Hori; Toshiya Teraishi; Miho Ota; Kotaro Hattori; Takamasa Noda; Ikki Ishida; Shigenobu Shibata; Hiroshi Kunugi

doi:10.1017/neu.2016.66

Association of body mass index-related single nucleotide polymorphisms with psychiatric disease and memory performance in a Japanese population

Published online by Cambridge University Press: 07 December 2016

Midori Ninomiya-Baba ,

Miho Ota ,

Ikki Ishida and

Midori Ninomiya-Baba: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan
Junko Matsuo: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan
Daimei Sasayama: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Japan
Hiroaki Hori: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan
Toshiya Teraishi: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan
Miho Ota: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan
Kotaro Hattori: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan
Takamasa Noda: Affiliation:
Department of Psychiatry, National Center of Neurology and Psychiatry Hospital, Tokyo, Japan
Ikki Ishida: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan
Shigenobu Shibata: Affiliation:
Laboratory of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan
Hiroshi Kunugi*: Affiliation:
Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, Tokyo, Japan
*: Hiroshi Kunugi, Director, Department of Mental Disorder Research, National Center of Neurology and Psychiatry, National Institute of Neuroscience, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan. Tel: +81 42 346 1714; Fax: +81 42 346 1714; E-mail: [email protected]

Article contents

Abstract
References

Get access

Rights & Permissions

Abstract

Objective

Obesity is a risk factor for psychiatric diseases. Recently, a number of single nucleotide polymorphisms (SNPs) have been shown to be related to body mass index (BMI). In this study, we investigated the association of BMI-related SNPs with psychiatric diseases and one of their endophenotypes, memory performance, in a Japanese population.

Methods

The subjects were 1624 patients with one of three psychiatric diseases (799 patients with major depressive disorder, 594 with schizophrenia, and 231 with bipolar disorder) and 1189 healthy controls. Memory performance was assessed using the Wechsler Memory Scale – Revised (WMS-R). Genomic DNA was prepared from venous blood and used to genotype 23 BMI-related SNPs using the TaqMan 5′-exonuclease allelic discrimination assay. We then analysed the relationships between the SNPs and psychiatric disease and various subscales of the WMS-R.

Results

Three SNPs (rs11142387, rs12597579, and rs6548238) showed significant differences in the genotype or allele frequency between patients with any psychiatric diseases and controls. Furthermore, six SNPs (rs11142387, rs12597579, rs2815752, rs2074356, rs4776970, and rs2287019) showed significant differences in at least one subscale of the WMS-R depending on the genotypes of the healthy controls. Interestingly, rs11142387 near the Kruppel-like factor 9 (KLF9) was significantly associated with psychiatric disease and poor memory function.

Conclusions

We identified three and six BMI-related SNPs associated with psychiatric disease and memory performance, respectively. In particular, carrying the A allele of rs11142387 near KLF9 was found to be associated with psychiatric disease and poor memory performance, which warrants further investigations.

Keywords

BMI memory psychiatric disorders SNP Wechsler Memory Scale – Revised

Type: Original Articles
Information: Acta Neuropsychiatrica , Volume 29 , Issue 5 , October 2017 , pp. 299 - 308

DOI: https://doi.org/10.1017/neu.2016.66 [Opens in a new window]
Copyright: © Scandinavian College of Neuropsychopharmacology 2016

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Stunkard, AJ, Faith, MS, Allison, KC. Depression and obesity. Biol Psychiatry 2003;54:330–337.Google Scholar

2. Manu, P, Dima, L, Shulman, M, Vancampfort, D, De Hert, M, Correll, CU. Weight gain and obesity in schizophrenia: epidemiology, pathobiology, and management. Acta Psychiatr Scand 2015;132:97–108.CrossRef Google Scholar PubMed

3. Mansur, RB, Brietzke, E, Mcintyre, RS. Is there a ‘metabolic-mood syndrome’? A review of the relationship between obesity and mood disorders. Neurosci Biobehav Rev 2015;52:89–104.Google Scholar

4. Luppino, FS, De Wit, LM, Bouvy, PF et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies. Arch Gen Psychiatry 2010;67:220–229.Google Scholar

5. Pan, A, Keum, N, Okereke, OI et al. Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care 2012;35:1171–1180.Google Scholar

6. Mcelroy, SL, Frye, MA, Suppes, T et al. Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry 2002;63:207–213.Google Scholar

7. Fagiolini, A, Kupfer, DJ, Houck, PR, Novick, DM, Frank, E. Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry 2003;160:112–117.Google Scholar

8. Calkin, C, Van De Velde, C, Ruzickova, M et al. Can body mass index help predict outcome in patients with bipolar disorder? Bipolar Disord 2009;11:650–656.Google Scholar

9. Deh, M, Schreurs, V, Vancampfort, D, Vanw, R. Metabolic syndrome in people with schizophrenia: a review. World Psychiatry 2009;8:15–22.Google Scholar

10. Meyer, JM, Nasrallah, HA, Mcevoy, JP et al. The clinical antipsychotic trials of intervention effectiveness (CATIE) schizophrenia trial: clinical comparison of subgroups with and without the metabolic syndrome. Schizophr Res 2005;80:9–18.CrossRef Google Scholar PubMed

11. Mitchell, AJ, Vancampfort, D, Sweers, K, Van Winkel, R, Yu, W, De Hert, M. Prevalence of metabolic syndrome and metabolic abnormalities in schizophrenia and related disorders – a systematic review and meta-analysis. Schizophr Bull 2013;39:306–318.Google Scholar

12. Sugawara, N, Yasui-Furukori, N, Sato, Y et al. Comparison of prevalence of metabolic syndrome in hospital and community-based Japanese patients with schizophrenia. Ann Gen Psychiatry 2011;10:21.CrossRef Google Scholar PubMed

13. Gunstad, J, Paul, RH, Cohen, RA, Tate, DF, Gordon, E. Obesity is associated with memory deficits in young and middle-aged adults. Eat Weight Disord 2006;11:e15–e19.Google Scholar

14. Kumari, M, Brunner, E, Fuhrer, R. Minireview: mechanisms by which the metabolic syndrome and diabetes impair memory. J Gerontol A Biol Sci Med Sci 2000;55:B228–B232.CrossRef Google Scholar PubMed

15. Baune, BT, Fuhr, M, Air, T, Hering, C. Neuropsychological functioning in adolescents and young adults with major depressive disorder – a review. Psychiatry Res 2014;218:261–271.Google Scholar

16. Martino, DJ, Samame, C, Ibanez, A, Strejilevich, SA. Neurocognitive functioning in the premorbid stage and in the first episode of bipolar disorder: a systematic review. Psychiatry Res 2015;226:23–30.CrossRef Google Scholar PubMed

17. Gur, RC, Gur, RE. Memory in health and in schizophrenia. Dialogues Clin Neurosci 2013;15:399–410.CrossRef Google Scholar PubMed

18. Bruce-Keller, AJ, Keller, JN, Morrison, CD. Obesity and vulnerability of the CNS. Biochim Biophys Acta 2009;1792:395–400.Google Scholar

19. Jagust, W, Harvey, D, Mungas, D, Haan, M. Central obesity and the aging brain. Arch Neurol 2005;62:1545–1548.Google Scholar

20. Wen, W, Cho, YS, Zheng, W et al. Meta-analysis identifies common variants associated with body mass index in east Asians. Nat Genet 2012;44:307–311.Google Scholar

21. Fall, T, Ingelsson, E. Genome-wide association studies of obesity and metabolic syndrome. Mol Cell Endocrinol 2014;382:740–757.Google Scholar

22. Okada, Y, Kubo, M, Ohmiya, H et al. Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations. Nat Genet 2012;44:302–306.Google Scholar

23. Xia, Q, Grant, SF. The genetics of human obesity. Ann N Y Acad Sci 2013;1281:178–190.Google Scholar

24. Flint, J, Kendler, KS. The genetics of major depression. Neuron 2014;81:484–503.CrossRef Google Scholar PubMed

25. Afari, N, Noonan, C, Goldberg, J et al. Depression and obesity: do shared genes explain the relationship? Depress Anxiety 2010;27:799–806.Google Scholar

26. Samaan, Z, Anand, SS, Zhang, X et al. The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression. Mol Psychiatry 2013;18:1281–1286.Google Scholar

27. Rivera, M, Cohen-Woods, S, Kapur, K et al. Depressive disorder moderates the effect of the FTO gene on body mass index. Mol Psychiatry 2012;17:604–611.Google Scholar

28. Gatt, JM, Burton, KL, Williams, LM, Schofield, PR. Specific and common genes implicated across major mental disorders: a review of meta-analysis studies. J Psychiatr Res 2015;60:1–13.Google Scholar

29. Cross-Disorder Group of the Psychiatric Genomics Consortium. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis. Lancet 2013;381:1371–1379.CrossRef Google Scholar

30. American Psychiatric Association. DSM-IV: Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Press, 1994.Google Scholar

31. Otsubo, T, Tanaka, K, Koda, R et al. Reliability and validity of Japanese version of the Mini-International Neuropsychiatric Interview. Psychiatry Clin Neurosci 2005;59:517–526.Google Scholar

32. Sheehan, DV, Lecrubier, Y, Sheehan, KH et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(Suppl 20):22–33. quiz 34–57.Google Scholar

33. Wechsler, D. Wechsler Adult Intelligence Scale, 3rd edn. NY, USA: Psychological Corporation, 1997.Google Scholar

34. Sugishita, M. [Japanese Wechsler Memory Scale, Revised], written in Japanese. Tokyo, Japan: Nihonbunka-kagakusha; 2001.Google Scholar

35. Pearson, R, Fleetwood, J, Eaton, S, Crossley, M, Bao, S. Kruppel-like transcription factors: a functional family. Int J Biochem Cell Biol 2008;40:1996–2001.CrossRef Google Scholar PubMed

36. Simmen, FA, Su, Y, Xiao, R, Zeng, Z, Simmen, RC. The Kruppel-like factor 9 (KLF9) network in HEC-1-A endometrial carcinoma cells suggests the carcinogenic potential of dys-regulated KLF9 expression. Reprod Biol Endocrinol 2008;6:41.Google Scholar

37. Zucker, SN, Fink, EE, Bagati, A et al. Nrf2 amplifies oxidative stress via induction of Klf9. Mol Cell 2014;53:916–928.Google Scholar

38. Lebrun, C, Avci, HX, Wehrle, R et al. Klf9 is necessary and sufficient for Purkinje cell survival in organotypic culture. Mol Cell Neurosci 2013;54:9–21.Google Scholar

39. Dugas, JC, Ibrahim, A, Barres, BA. The T3-induced gene KLF9 regulates oligodendrocyte differentiation and myelin regeneration. Mol Cell Neurosci 2012;50:45–57.CrossRef Google Scholar PubMed

40. Mighdoll, MI, Tao, R, Kleinman, JE, Hyde, TM. Myelin, myelin-related disorders, and psychosis. Schizophr Res 2015;161:85–93.Google Scholar

41. Fields, RD. White matter in learning, cognition and psychiatric disorders. Trends Neurosci 2008;31:361–370.CrossRef Google Scholar PubMed

42. Zhang, Y, Zhang, H, Wang, L et al. Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination. Schizophr Res 2012;138:8–17.Google Scholar

43. Hoops, TC, Ivanov, I, Cui, Z, Colomer-Gould, V, Rindler, MJ. Incorporation of the pancreatic membrane protein GP-2 into secretory granules in exocrine but not endocrine cells. J Biol Chem 1993;268:25694–25705.Google Scholar

44. Gomez-Lazaro, M, Rinn, C, Aroso, M, Amado, F, Schrader, M. Proteomic analysis of zymogen granules. Expert Rev Proteomics 2010;7:735–747.Google Scholar

45. Somma, V, Ababneh, H, Ababneh, A et al. The Novel Crohn’s Disease Marker Anti-GP2 Antibody Is Associated with Ileocolonic Location of Disease. Gastroenterol Res Pract 2013;2013:683824.Google Scholar

46. Thorleifsson, G, Walters, GB, Gudbjartsson, DF et al. Genome-wide association yields new sequence variants at seven loci that associate with measures of obesity. Nat Genet 2009;41:18–24.Google Scholar

47. Rohde, K, Keller, M, Klos, M et al. Adipose tissue depot specific promoter methylation of TMEM18. J Mol Med (Berl) 2014;92:881–888.CrossRef Google Scholar PubMed

48. Almen, MS, Jacobsson, JA, Shaik, JH et al. The obesity gene, TMEM18, is of ancient origin, found in majority of neuronal cells in all major brain regions and associated with obesity in severely obese children. BMC Med Genet 2010;11:58.Google Scholar

49. Jurvansuu, J, Zhao, Y, Leung, DS et al. Transmembrane protein 18 enhances the tropism of neural stem cells for glioma cells. Cancer Res 2008;68:4614–4622.Google Scholar

50. Hotta, K, Nakamura, M, Nakamura, T et al. Association between obesity and polymorphisms in SEC16B, TMEM18, GNPDA2, BDNF, FAIM2 and MC4R in a Japanese population. J Hum Genet 2009;54:727–731.CrossRef Google Scholar

51. Marg, A, Sirim, P, Spaltmann, F et al. Neurotractin, a novel neurite outgrowth-promoting Ig-like protein that interacts with CEPU-1 and LAMP. J Cell Biol 1999;145:865–876.Google Scholar

52. Lee, AW, Hengstler, H, Schwald, K et al. Functional inactivation of the genome-wide association study obesity gene neuronal growth regulator 1 in mice causes a body mass phenotype. PLoS One 2012;7:e41537.Google Scholar

53. Speliotes, EK, Willer, CJ, Berndt, SI et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010;42:937–948.Google Scholar

54. Willer, CJ, Speliotes, EK, Loos, RJ et al. Six new loci associated with body mass index highlight a neuronal influence on body weight regulation. Nat Genet 2009;41:25–34.Google Scholar

55. Dennis, EL, Jahanshad, N, Braskie, MN et al. Obesity gene NEGR1 associated with white matter integrity in healthy young adults. Neuroimage 2014;102(Pt 2):548–557.Google Scholar

56. Kim, YJ, Go, MJ, Hu, C et al. Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. Nat Genet 2011;43:990–995.Google Scholar

57. Heo, SG, Hwang, JY, Uhmn, S et al. Male-specific genetic effect on hypertension and metabolic disorders. Hum Genet 2014;133:311–319.CrossRef Google Scholar PubMed

58. Drew, BA, Burow, ME, Beckman, BS. MEK5/ERK5 pathway: the first fifteen years. Biochim Biophys Acta 2012;1825:37–48.Google Scholar

59. Wang, W, Pan, YW, Zou, J et al. Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory. J Neurosci 2014;34:2130–2147.Google Scholar

60. Becker, A, Eichentopf, R, Sedlmeier, R et al. IsoQC (QPCTL) knock-out mice suggest differential substrate conversion by glutaminyl cyclase isoenzymes. Biol Chem 2016;397:45–55.Google Scholar

61. Saido, TC, Iwatsubo, T, Mann, DM, Shimada, H, Ihara, Y, Kawashima, S. Dominant and differential deposition of distinct beta-amyloid peptide species, A beta N3(pE), in senile plaques. Neuron 1995;14:457–466.Google Scholar

62. Flatt, PR. Dorothy Hodgkin Lecture 2008. Gastric inhibitory polypeptide (GIP) revisited: a new therapeutic target for obesity-diabetes? Diabet Med 2008;25:759–764.Google Scholar

63. Irwin, N, Flatt, PR. Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia 2009;52:1724–1731.CrossRef Google Scholar PubMed

64. Lennox, R, Moffett, RC, Porter, DW, Irwin, N, Gault, VA, Flatt, PR. Effects of glucose-dependent insulinotropic polypeptide receptor knockout and a high-fat diet on cognitive function and hippocampal gene expression in mice. Mol Med Rep 2015;12:1544–1548.Google Scholar