Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and meta-analysis

Agerbo, Esben, Sullivan, Patrick F., Vilhjalmsson, Bjarni J., Pedersen, Catsten B., Mors, Ole, Borglum, Anders D., Hougaard, David M., Hollegaard, Mads V., Meier, Sandra, Mattheisen, Manuel, Ripke, Stephen, Wray, Naomi R. and Mortensen, Preben B. (2015) Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and meta-analysis. JAMA Psychiatry, 72 7: 635-641. doi:10.1001/jamapsychiatry.2015.0346

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Author Agerbo, Esben
Sullivan, Patrick F.
Vilhjalmsson, Bjarni J.
Pedersen, Catsten B.
Mors, Ole
Borglum, Anders D.
Hougaard, David M.
Hollegaard, Mads V.
Meier, Sandra
Mattheisen, Manuel
Ripke, Stephen
Wray, Naomi R.
Mortensen, Preben B.
Title Polygenic risk score, parental socioeconomic status, family history of psychiatric disorders, and the risk for schizophrenia: a Danish population-based study and meta-analysis
Journal name JAMA Psychiatry   Check publisher's open access policy
ISSN 2168-622X
2168-6238
Publication date 2015-07-01
Sub-type Article (original research)
DOI 10.1001/jamapsychiatry.2015.0346
Open Access Status File (Publisher version)
Volume 72
Issue 7
Start page 635
End page 641
Total pages 7
Publisher American Medical Association
Language eng
Formatted abstract
Importance:   Schizophrenia has a complex etiology influenced both by genetic and nongenetic factors but disentangling these factors is difficult.

Objective:   To estimate (1) how strongly the risk for schizophrenia relates to the mutual effect of the polygenic risk score, parental socioeconomic status, and family history of psychiatric disorders; (2) the fraction of cases that could be prevented if no one was exposed to these factors; (3) whether family background interacts with an individual’s genetic liability so that specific subgroups are particularly risk prone; and (4) to what extent a proband’s genetic makeup mediates the risk associated with familial background.

Design, settings, and participants:   We conducted a nested case-control study based on Danish population-based registers. The study consisted of 866 patients diagnosed as having schizophrenia between January 1, 1994, and December 31, 2006, and 871 matched control individuals. Genome-wide data and family psychiatric and socioeconomic background information were obtained from neonatal biobanks and national registers. Results from a separate meta-analysis (34 600 cases and 45 968 control individuals) were applied to calculate polygenic risk scores.

Exposures:   Polygenic risk scores, parental socioeconomic status, and family psychiatric history.

Main outcomes and measures:   Odds ratios (ORs), attributable risks, liability R2 values, and proportions mediated.

Results:   Schizophrenia was associated with the polygenic risk score (OR, 8.01; 95% CI, 4.53-14.16 for highest vs lowest decile), socioeconomic status (OR, 8.10; 95% CI, 3.24-20.3 for 6 vs no exposures), and a history of schizophrenia/psychoses (OR, 4.18; 95% CI, 2.57-6.79). The R2 values were 3.4% (95% CI, 2.1-4.6) for the polygenic risk score, 3.1% (95% CI, 1.9-4.3) for parental socioeconomic status, and 3.4% (95% CI, 2.1-4.6) for family history. Socioeconomic status and psychiatric history accounted for 45.8% (95% CI, 36.1-55.5) and 25.8% (95% CI, 21.2-30.5) of cases, respectively. There was an interaction between the polygenic risk score and family history (P = .03). A total of 17.4% (95% CI, 9.1-26.6) of the effect associated with family history of schizophrenia/psychoses was mediated through the polygenic risk score.

Conclusions and Relevance:  Schizophrenia was associated with the polygenic risk score, family psychiatric history, and socioeconomic status. Our study demonstrated that family history of schizophrenia/psychoses is partly mediated through the individual’s genetic liability.
Keyword Schizophrenia
Denmark
Genetic factors
Parental socioeconomic status
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
 
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Citation counts: TR Web of Science Citation Count  Cited 38 times in Thomson Reuters Web of Science Article | Citations
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