Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-02T22:15:48.775Z Has data issue: false hasContentIssue false
  • English
  • Français

Do genetic risk scores for body mass index predict risk of phobic anxiety? Evidence for a shared genetic risk factor

Published online by Cambridge University Press:  28 May 2014

S. Walter ,
M. M. Glymour ,
K. Koenen ,
L. Liang ,
E. J. Tchetgen Tchetgen ,
M. Cornelis ,
S.-C. Chang ,
M. Rewak ,
E. Rimm  and
I. Kawachi
...Show all authors
S. Walter*
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
M. M. Glymour
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA
K. Koenen
Affiliation:
Mailman School of Public Health, Columbia University, New York, NY, USA
L. Liang
Affiliation:
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
E. J. Tchetgen Tchetgen
Affiliation:
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Biostatistics, Harvard School of Public Health, Boston, MA, USA
M. Cornelis
Affiliation:
Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
S.-C. Chang
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
M. Rewak
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
E. Rimm
Affiliation:
Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA Department of Nutrition, Harvard School of Public Health, Boston, MA, USA
I. Kawachi
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
L. D. Kubzansky
Affiliation:
Department of Social and Behavioral Sciences, Harvard School of Public Health, Boston, MA, USA
*
*Address for correspondence: S. Walter, Ph.D., Department of Social and Behavioral Sciences, Harvard School of Public Health, Landmark Center, 445-C, 401 Park Drive, Boston, MA 02215, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Obesity and anxiety are often linked but the direction of effects is not clear.

Method

Using genetic instrumental variable (IV) analyses in 5911 female participants from the Nurses' Health Study (NHS, initiated 1976) and 3697 male participants from the Health Professional Follow-up Study (HPFS, initiated 1986), we aimed to determine whether obesity increases symptoms of phobic anxiety. As instrumental variables we used the fat mass and obesity-associated (FTO) gene, the melanocortin 4 receptor (MC4R) gene and a genetic risk score (GRS) based on 32 single nucleotide polymorphisms (SNPs) that significantly predict body mass index (BMI). ‘Functional’ GRSs corresponding with specific biological pathways that shape BMI (adipogenesis, appetite and cardiopulmonary) were considered. The main outcome was phobic anxiety measured by the Crown Crisp Index (CCI) in 2004 in the NHS and in 2000 in the HPFS.

Results

In observational analysis, a 1-unit higher BMI was associated with higher phobic anxiety symptoms [women: β = 0.05, 95% confidence interval (CI) 0.030–0.068; men: β = 0.04, 95% CI 0.016–0.071). IV analyses showed that BMI was associated with higher phobic anxiety symptoms in the FTO-instrumented analysis (p = 0.005) but not in the GRS-instrumented analysis (p = 0.256). Functional GRSs showed heterogeneous, non-significant effects of BMI on phobic anxiety symptoms.

Conclusions

Our findings do not provide conclusive evidence in favor of the hypothesis that higher BMI leads to higher levels of phobic anxiety, but rather suggest that genes that influence obesity, in particular FTO, may have direct effects on phobic anxiety, and hence that obesity and phobic anxiety may share common genetic determinants.

Keywords

Anxietybody mass indexFTOgeneticsMendelian randomization analysisphobic anxiety
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 1 , January 2015 , pp. 181 - 191
Copyright
Copyright © Cambridge University Press 2014 

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

Albert, CM, Chae, CU, Rexrode, KM, Manson, JAE, Kawachi, I (2005). Phobic anxiety and risk of coronary heart disease and sudden cardiac death among women. Circulation 111, 480–487.Google Scholar
Angrist, JD, Krueger, AB (1994). Split Sample Instrumental Variables. Technical Working Paper No. 150. National Bureau of Economic Research: Cambridge, MA.Google Scholar
Angrist, JD, Krueger, AB (1995). Split-sample instrumental variables estimates of the return to schooling. Journal of Business and Economic Statistics 13, 225–235.Google Scholar
Bjerkeset, O, Romundstad, P, Evans, J, Gunnell, D (2008). Association of adult body mass index and height with anxiety, depression, and suicide in the general population: the HUNT study. American Journal of Epidemiology 167, 193–202.Google Scholar
Bodenlos, JS, Lemon, SC, Schneider, KL, August, MA, Pagoto, SL (2011). Associations of mood and anxiety disorders with obesity: comparisons by ethnicity. Journal of Psychosomatic Research 71, 319–324.CrossRefGoogle ScholarPubMed
Bowden, J, Vansteelandt, S (2011). Mendelian randomization analysis of case-control data using structural mean models. Statistics in Medicine 30, 678–694.CrossRefGoogle ScholarPubMed
Cairney, J, Corna, LM, Veldhuizen, S, Kurdyak, P, Streiner, DL (2008). The social epidemiology of affective and anxiety disorders in later life in Canada. Canadian Journal of Psychiatry 53, 104–111.CrossRefGoogle ScholarPubMed
Chu, NF, Stampfer, MJ, Spiegelman, D, Rifai, N, Hotamisligil, GS, Rimm, EB (2001). Dietary and lifestyle factors in relation to plasma leptin concentrations among normal weight and overweight men. International Journal of Obesity 25, 106–114.Google Scholar
Colditz, GA, Hankinson, SE (2005). The Nurses’ Health Study: lifestyle and health among women. Nature Reviews Cancer 5, 388–396.CrossRefGoogle ScholarPubMed
Crisp, A, Jones, MG, Slater, P (1978). The Middlesex Hospital Questionnaire: a validity study. British Journal of Medical Psychology 51, 269–280.Google Scholar
Crown, S, Crisp, AH (1966). A short clinical diagnostic self-rating scale for psychoneurotic patients. The Middlesex Hospital Questionnaire (M.H.Q.). British Journal of Psychiatry 112, 917–923.CrossRefGoogle Scholar
Domschke, K, Reif, A (2012). Behavioral genetics of affective and anxiety disorders. Current Topics in Behavioral Neurosciences 12, 463–502.Google Scholar
Gariepy, G, Nitka, D, Schmitz, N (2010). The association between obesity and anxiety disorders in the population: a systematic review and meta-analysis. International Journal of Obesity 34, 407–419.CrossRefGoogle ScholarPubMed
Glymour, MM, Tchetgen Tchetgen, EJ, Robins, JM (2012). Credible Mendelian randomization studies: approaches for evaluating the instrumental variable assumptions. American Journal of Epidemiology 175, 332–339.Google Scholar
Haines, AP, Imeson, JD, Meade, TW (1987). Phobic anxiety and ischaemic heart disease. British Medical Journal (Clinical Research Edition) 295, 297–299.CrossRefGoogle ScholarPubMed
Hettema, JM, Neale, MC, Kendler, KS (2001). A review and meta-analysis of the genetic epidemiology of anxiety disorders. American Journal of Psychiatry 158, 1568–1578.CrossRefGoogle ScholarPubMed
Hettema, JM, Prescott, CA, Myers, JM, Neale, MC, Kendler, KS (2005). The structure of genetic and environmental risk factors for anxiety disorders in men and women. Archives of General Psychiatry 62, 182–189.Google Scholar
Irvine, J, Firestone, J, Ong, L, Cribbie, R, Dorian, P, Harris, L, Ritvo, P, Katz, J, Newman, D, Cameron, D (2011). A randomized controlled trial of cognitive behavior therapy tailored to psychological adaptation to an implantable cardioverter defibrillator. Psychosomatic Medicine 73, 226–233.CrossRefGoogle Scholar
Jokela, M, Elovainio, M, Keltikangas-Järvinen, L, David Batty, G, Hintsanen, M, Seppälä, I, Kähönen, M, Viikari, JS, Raitakari, OT, Lehtimäki, T (2012). Body mass index and depressive symptoms: instrumental-variables regression with genetic risk score. Genes, Brain and Behavior. Published online: 7 September 2012 . doi:10.1111/j.1601-183X.2012.00846.x.Google Scholar
Kawachi, I, Colditz, GA, Ascherio, A, Rimm, EB, Giovannucci, E, Stampfer, MJ, Willett, WC (1994). Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 89, 1992–1997.Google Scholar
Kessler, RC, Aguilar-Gaxiola, S, Alonso, J, Chatterji, S, Lee, S, Ormel, J, Ustun, TB, Wang, PS (2009). The global burden of mental disorders: an update from the WHO World Mental Health (WMH) surveys. Epidemiologia e psichiatria sociale 18, 23–33.Google Scholar
Kessler, RC, Berglund, P, Demler, O, Jin, R, Merikangas, KR, Walters, EE (2005). Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry 62, 593–602.Google Scholar
Kessler, RC, Petukhova, M, Sampson, NA, Zaslavsky, AM, Wittchen, HU (2012). Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. International Journal of Methods in Psychiatric Research 21, 169–184.Google Scholar
Kivimaki, M, Jokela, M, Hamer, M, Geddes, J, Ebmeier, K, Kumari, M, Singh-Manoux, A, Hingorani, A, Batty, GD (2011). Examining overweight and obesity as risk factors for common mental disorders using fat mass and obesity-associated (FTO) genotype-instrumented analysis: the Whitehall II Study, 1985–2004. American Journal of Epidemiology 173, 421–429.CrossRefGoogle ScholarPubMed
Lawlor, DA, Harbord, RM, Tybjaerg Hansen, A, Palmer, TM, Zacho, J, Benn, M, Timpson, NJ, Davey Smith, G, Nordestgaard, BG (2011). Using genetic loci to understand the relationship between adiposity and psychological distress: a Mendelian Randomization study in the Copenhagen General Population Study of 53,221 adults. Journal of Internal Medicine 269, 525–537.CrossRefGoogle Scholar
Leis, JA, Heron, J, Stuart, EA, Mendelson, T (2014). Associations between maternal mental health and child emotional and behavioral problems: does prenatal mental health matter? Journal of Abnormal Child Psychology 42, 161–171.Google Scholar
Mavissakalian, M, Michelson, L (1981). The Middlesex Hospital Questionnaire: a validity study with American psychiatric patients. Britisch Journal of Psychiatry 139, 336–340.Google Scholar
Nousen, EK, Franco, JG, Sullivan, EL (2013). Unraveling the mechanisms responsible for the comorbidity between metabolic syndrome and mental health disorders. Neuroendocrinology 98, 254–266.CrossRefGoogle ScholarPubMed
Oldroyd, JC, Cyril, S, Wijayatilaka, BS, O'Neil, A, McKenzie, DP, Zavarsek, S, Sanderson, K, Hare, DL, Fisher, AJ, Forbes, AB, Barr Taylor, C, Clarke, DM, Meredith, IT, Oldenburg, B (2013). Evaluating the impact of depression, anxiety & autonomic function on health related quality of life, vocational functioning and health care utilisation in acute coronary syndrome patients: the ADVENT study protocol. BMC Cardiovascular Disorders 13, 103.Google Scholar
Price, AL, Patterson, NJ, Plenge, RM, Weinblatt, ME, Shadick, NA, Reich, D (2006). Principal components analysis corrects for stratification in genome-wide association studies. Nature Genetics 38, 904–909.Google Scholar
Purcell, SM, Wray, NR, Stone, JL, Visscher, PM, O'Donovan, MC, Sullivan, PF, Sklar, P, Ruderfer, DM, McQuillin, A, Morris, DW (2009). Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460, 748–752.Google Scholar
Rimm, EB, Stampfer, MJ, Colditz, GA, Chute, CG, Litin, LB, Willett, WC (1990). Validity of self-reported waist and hip circumferences in men and women. Epidemiology 1, 466–73.Google Scholar
Samaan, Z, Anand, SS, Zhang, X, Desai, D, Rivera, M, Pare, G, Thabane, L, Xie, C, Gerstein, H, Engert, JC, Craig, I, Cohen-Woods, S, Mohan, V, Diaz, R, Wang, X, Liu, L, Corre, T, Preisig, M, Kutalik, Z, Bergmann, S, Vollenweider, P, Waeber, G, Yusuf, S, Meyre, D (2013). The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression. Molecular Psychiatry 18, 1281–1286.Google Scholar
Sareen, J, Cox, BJ, Clara, I, Asmundson, GJ (2005). The relationship between anxiety disorders and physical disorders in the US National Comorbidity Survey. Depression and Anxiety 21, 193–202.Google Scholar
Smoller, JW (2011). Who's afraid of anxiety genetics? Biological Psychiatry 69, 506–507.CrossRefGoogle ScholarPubMed
Smoller, JW, Gardner-Schuster, E, Covino, J (2008). The genetic basis of panic and phobic anxiety disorders. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics 148C, 118–126.Google Scholar
Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Mägi, R (2010). Association analyses of 2 49 796 individuals reveal 18 new loci associated with body mass index. Nature Genetics 42, 937–948.Google Scholar
Tchetgen Tchetgen, EJ, Walter, S, Glymour, MM (2013). Commentary: building an evidence base for mendelian randomization studies: assessing the validity and strength of proposed genetic instrumental variables. International Journal of Epidemiology 42, 328–331.Google Scholar
VanderWeele, TJ (2012). Invited commentary: structural equation models and epidemiologic analysis. American Journal of Epidemiology 176, 608–612.Google Scholar
Young, JPR, Fenton, GW, Lader, MH (1971). The inheritance of neurotic traits: a twin study of the Middlesex Hospital Questionnaire. British Journal of Psychiatry 119, 393–398.Google Scholar
Supplementary material: File

Walter Supplementary Material

Supplementary Information

Download Walter Supplementary Material(File)
File 159.7 KB