Preben Bo Mortensen

Absolute risk of major depression associated with the polygenic risk score for depression, parental socio-economic status and history of mental disorders: A danish population-based study

Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

  • Esben Agerbo
  • Betina B Trabjerg
  • Andrew J Schork, Mental Health Center Sct. Hans
  • ,
  • Bjarni Jóhann Vilhjálmsson
  • Clara Albiñana Climent
  • Naomi R. Wray, Univ Queensland, University of Queensland, Queensland Brain Inst, The University of Queensland
  • ,
  • Thomas Werge, Mental Health Center Sct. Hans, H. Lundbeck A/S, Københavns Universitet, Institute of Biological Psychiatry, Danmark
  • Anders Børglum
  • Ole Mors, Centre for Psychiatric Research, Aarhus University Hospital, Risskov, Skovagervej 2, 8240 Risskov, Denmark., Danmark
  • Merete Nordentoft, Psychiatric Centre Copenhagen, Danmark
  • David Hougaard, Statens Seruminstitut, København
  • ,
  • Katherine Musliner
  • Preben Bo Mortensen
  • John J McGrath, Queensland Brain Institute, University of Queensland, St Lucia, Australia2Queensland Centre for Mental Health Research, The Park Centre for Mental Health, Richlands, Australia.
Background: Major depression (MD) is debilitating and complex disorder with an absolute risk before age 30 years of 6.0% and 2.7% and with a lifetime risk of 15.5% and 9.1% for females and males, respectively. Our aim is to predict absolute risk of depression as a function of age for individuals with various MD genetic liabilities who grow up in families characterized by various socioeconomic statuses and histories of mental disorders.

Methods: Data were obtained by using the Danish Civil Registration System (DCPR). The iPSYCH2012 sample is nested with the DCRS, as a population-based case-cohort sample consisting of individuals (N=88,764) who were born between May 1981 and December 2005 (N=1,472,762). Frozen blood spots for almost all neonates were stored in the Danish Neonatal Screening Biobank during this period.

The iPSYCH2012 sample consists of uniform random sub-cohort with 30,000 individuals, and of all individuals diagnosed with specific psychiatric disorders between January 1, 1994 and December 31, 2012. MD was defined as ICD10:F32-33.

Polygenic risk scores (PRS) using recent MD summary statistics were used. Parental socio-economic status and psychiatric history were obtained from registers.

Cox proportional regression models for case-cohort data were used to estimate hazard ratios and absolute risk of major depression as a function of age (10-30 yrs). The number of individuals needed to have their exposure counterfactually altered to prevent one additional MD case before age 30 years were calculated. The proportion of familial risk mediated through the PRS was estimated.

Results: The sample consisted of 18427 major depression cases and 20161 sub-cohort individuals.

As expected, the MD hazard ratio increased with increasing PRS liability, maternal or paternal history of depression and psychiatric disorders, and among those with lower parental socio-economic status. No statistical interaction between the polygenic risk score and parental psychiatric disorders (P=0.5) or parental socio-economic status were detected (P=0.6).

Regarding the absolute risk, 31.9% (95%CI, 9.9%-103.2%) of females who have the highest 2% polygenic liability and whose parents both have suffered from a psychiatric disorder will be diagnosed with major depression before age 30 years. The corresponding percentage associated with the lowest 2% PRS and no parental psychiatric history is 3.0% (2.7%-3.4%). If it was hypothetically imagined, that high-risk females could be treated, so that they had the same risk as females with lowest risk, only 3-4 females needed to be treated to prevent one case of depression (i.e. 3.5 [95%CI, 3.0-3.9]). Analogous but less pronounced findings are seen for males.

Discussion: Our study is one of the first to report absolute risk of depression as a function of age in relation to the interplay between PRS for MD, parental SES and histories of psychiatric disorders.

The recent success of polygenic risk scores has entailed a pronounced enthusiasm, and furthermore, some studies anticipated that it might be clinically possible to mitigate risk years or decades in advance. It is, however, widely recognised that polygenic predictions are not particularly informative for an individual, and that PRSs are not yet clinically useful in major depression.

Our study shows that combining a PRS with family-based factor may years in advance predict groups at high risk of depression.
OriginalsprogEngelsk
Udgivelsesår1 okt. 2019
StatusUdgivet - 1 okt. 2019
BegivenhedWorld Congress of Psychiatric Genetics - Anaheim , USA
Varighed: 26 okt. 201931 okt. 2019

Konference

KonferenceWorld Congress of Psychiatric Genetics
LandUSA
ByAnaheim
Periode26/10/201931/10/2019

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