Hostname: page-component-76fb5796d-5g6vh Total loading time: 0 Render date: 2024-04-27T09:58:10.394Z Has data issue: false hasContentIssue false
  • English
  • Français

Impact of comorbidity on family genetic risk profiles for psychiatric and substance use disorders: a descriptive analysis

Published online by Cambridge University Press:  22 November 2021

Kenneth S. Kendler Open the ORCID record for Kenneth S. Kendler [Opens in a new window] ,
Henrik Ohlsson ,
Jan Sundquist  and
Kristina Sundquist
Kenneth S. Kendler*
Affiliation:
Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA
Henrik Ohlsson
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden
Jan Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA
Kristina Sundquist
Affiliation:
Center for Primary Health Care Research, Lund University, Malmö, Sweden Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA
*
Author for correspondence: Kenneth S. Kendler, E-mail: Kenneth.Kendler@vcuhealth.org
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

– Comorbidity between psychiatric disorders is extensive but, from a genetic perspective, still poorly understood. Modern molecular genetic approaches to this problem are limited by a reliance on case–control designs.

Methods

– In 5 828 760 individuals born in Sweden from 1932–1995 with a mean (s.d.) age at follow-up of 54.4 (18.1), we examined family genetic risk score (FGRS) profiles including internalizing, psychotic, substance use and developmental disorders in 10 pairs of psychiatric and substance use disorders diagnosed from population registries. We examined these profiles in three groups of patients: disorder A only, disorder B only and comorbid cases with both disorders.

Results

– The most common pattern of findings, seen in five pairings, was simple and quantitative. Comorbid cases had higher FGRS than both non-comorbid cases for all (or nearly all) disorders. However, the pattern was more complex in the remaining five pairings and included qualitative changes where the comorbid cases showed no increases in FGRS for certain disorders and in a few cases significant decreases. Several comparisons showed an asymmetric pattern of findings with increases, in comorbidity compared to single disorder cases, of the FGRS for only one of the two disorders.

Conclusions

– The examination of FGRS profiles in general population samples where all disorders are assessed in all subjects provides a fruitful line of inquiry to understand the origins of psychiatric comorbidity. Further work will be needed, with an expansion of analytic approaches, to gain deeper insights into the complex mechanisms likely involved.

Keywords

Comorbiditypsychiatric and substance use disordersfamily genetic risk scoresmechanisms
Type
Original Article
Information
Psychological Medicine , Volume 53 , Issue 6 , April 2023 , pp. 2389 - 2398
Check for updates
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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

Bulik, C. M., Thornton, L. M., Root, T. L., Pisetsky, E. M., Lichtenstein, P., & Pedersen, N. L. (2010). Understanding the relation between anorexia nervosa and bulimia nervosa in a Swedish national twin sample. Biological Psychiatry, 67, 71–77.CrossRefGoogle Scholar
Consortium(PGC-CDG), C.-D. G. o. t. P. G. (2013). Genetic relationship between five psychiatric disorders estimated from genome-wide SNPs. Nature Genetics, 45, 984–994.CrossRefGoogle Scholar
Cross-Disorder Group of the Psychiatric Genomics Consortium (2019). Genomic relationships, novel loci, and pleiotropic mechanisms across eight psychiatric disorders. Cell, 179, 1469–1482.e11.CrossRefGoogle Scholar
Ekholm, B., Ekholm, A., Adolfsson, R., Vares, M., Osby, U., Sedvall, G. C., & Jonsson, E. G. (2005). Evaluation of diagnostic procedures in Swedish patients with schizophrenia and related psychoses. Nordic Journal of Psychiatry, 59, 457–464.CrossRefGoogle ScholarPubMed
Hujoel, M. L., Gazal, S., Loh, P.-R., Patterson, N., & Price, A. L. (2020). Liability threshold modeling of case–control status and family history of disease increases association power. Nature Genetics, 52, 541–547.CrossRefGoogle ScholarPubMed
Kendler, K., Ohlsson, H., Sundquist, J., & Sundquist, K. (In press). The impact of sex, age at onset, recurrence, mode of ascertainment and medical complications on the family genetic risk score profiles for alcohol use disorder. Psychological Medicine.Google Scholar
Kendler, K. S., Aggen, S. H., Knudsen, G. P., Roysamb, E., Neale, M. C., & Reichborn-Kjennerud, T. (2011). The structure of genetic and environmental risk factors for syndromal and subsyndromal common DSM-IV axis I and All axis II disorders. American Journal of Psychiatry, 168, 29–39.CrossRefGoogle ScholarPubMed
Kendler, K. S., Ji, J., Edwards, A. C., Ohlsson, H., Sundquist, J., & Sundquist, K. (2015). An extended Swedish national adoption study of alcohol use disorder. JAMA Psychiatry, 72, 211–218.CrossRefGoogle ScholarPubMed
Kendler, K. S., Maes, H. H., Sundquist, K., Ohlsson, H., & Sundquist, J. (2013). Genetic and family and community environmental effects on drug abuse in adolescence: A Swedish national twin and sibling study. American Journal of Psychiatry, 171, 209–217.CrossRefGoogle Scholar
Kendler, K. S., Ohlsson, H., Lichtenstein, P., Sundquist, J., & Sundquist, K. (2018). The genetic epidemiology of treated major depression in Sweden. American Journal of Psychiatry, 175, 1137–1144.CrossRefGoogle ScholarPubMed
Kendler, K. S., Ohlsson, H., Sundquist, J., & Sundquist, K. (2021a). Family genetic risk scores and the genetic architecture of major affective and psychotic disorders in a Swedish national sample. JAMA Psychiatry, 78, 735–743.CrossRefGoogle Scholar
Kendler, K. S., Ohlsson, H., Sundquist, J., & Sundquist, K. (2021b). The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample. Translational Psychiatry, 11, 1–8.CrossRefGoogle Scholar
Kendler, K. S., PirouziFard, M., Lonn, S., Edwards, A. C., Maes, H. H., Lichtenstein, P., … Sundquist, K. (2016). A national Swedish twin-sibling study of alcohol use disorders. Twin Research and Human Genetics, 19, 430–437.CrossRefGoogle ScholarPubMed
Kendler, K. S., Sundquist, K., Ohlsson, H., Palmer, K., Maes, H., Winkleby, M. A., & Sundquist, J. (2012). Genetic and familial environmental influences on the risk for drug abuse: A national Swedish adoption study. Archive of General Psychiatry, 69, 690–697.CrossRefGoogle ScholarPubMed
Kessler, R. C. (1997). The prevalence of psychiatric comorbidity. In Wetzler, S., & Sanderson, W. C. (Eds.), Treatment strategies for patients with psychiatric comorbidity (pp. 23–48). New York, NY: John Wiley & Sons, Inc.Google Scholar
Kessler, R. C., Chiu, W. T., Demler, O., Merikangas, K. R., & Walters, E. E. (2005). Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. Archives of General Psychiatry, 62, 617–627.CrossRefGoogle ScholarPubMed
Kessler, R. C., McGonagle, K. A., Carnelley, K. B., Nelson, C. B., Farmer, M., & Regier, D. A. (1993). Comorbidity of mental disorders and substance abuse disorders: A review and agenda for future research. In Leaf, P. J. (ed.), Research in community and mental health). Greenwich, CT: JAI Press.Google Scholar
Kessler, R. C., Ormel, J., Petukhova, M., McLaughlin, K. A., Green, J. G., Russo, L. J., … Ustun, T. B. (2011). Development of lifetime comorbidity in the World Health Organization world mental health surveys. Archives of General Psychiatry, 68, 90–100.CrossRefGoogle ScholarPubMed
Klein, D. N., & Riso, L. P. (1993). Psychiatric disorders: Problems of boundaries and comorbidity. In Costello, C. G. (Ed.), Basic issues in psychopathology (pp. 19–66). New York: Guilford Press.Google Scholar
Lichtenstein, P., Bjork, C., Hultman, C. M., Scolnick, E., Sklar, P., & Sullivan, P. F. (2006). Recurrence risks for schizophrenia in a Swedish national cohort. Psychological Medicine, 36, 1417–1425.CrossRefGoogle Scholar
Neale, M. C., & Kendler, K. S. (1995). Models of comorbidity for multifactorial disorders. American Journal of Human Genetics, 57, 935–953.Google ScholarPubMed
Rück, C., Larsson, K. J., Lind, K., Perez-Vigil, A., Isomura, K., Sariaslan, A., … Mataix-Cols, D. (2015). Validity and reliability of chronic tic disorder and obsessive-compulsive disorder diagnoses in the Swedish National Patient Register. BMJ Open, 5, e007520.CrossRefGoogle ScholarPubMed
SAS Institute, I. (2012). SAS/STAT® online documentation, version 9.4. Cary, N.C.: SAS Institute, Inc.Google Scholar
Sellgren, C., Landen, M., Lichtenstein, P., Hultman, C. M., & Langstrom, N. (2011). Validity of bipolar disorder hospital discharge diagnoses: File review and multiple register linkage in Sweden. Acta Psychiatrica Scandnavica, 124, 447–453.CrossRefGoogle ScholarPubMed
Slutske, W. S., Eisen, S., True, W. R., Lyons, M. J., Goldberg, J., & Tsuang, M. (2000). Common genetic vulnerability for pathological gambling and alcohol dependence in men. Archives of General Psychiatry, 57, 666–673.CrossRefGoogle ScholarPubMed
Smoller, J. W., Andreassen, O. A., Edenberg, H. J., Faraone, S. V., Glatt, S. J., & Kendler, K. S. (2019). Psychiatric genetics and the structure of psychopathology. Molecular Psychiatry, 24, 409–420.CrossRefGoogle ScholarPubMed
Sundquist, J., Ohlsson, H., Sundquist, K., & Kendler, K. S. (2017). Common adult psychiatric disorders in Swedish primary care (where most mental health patients are treated). BMC Psychiatry, 17, 235.CrossRefGoogle ScholarPubMed
Waldman, I. D., Poore, H. E., Luningham, J. M., & Yang, J. (2020). Testing structural models of psychopathology at the genomic level. World Psychiatry, 19, 350–359.CrossRefGoogle ScholarPubMed
Supplementary material: File

Kendler et al. supplementary material

Appendix

Download Kendler et al. supplementary material(File)
File 2.1 MB