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Abstract:
An association between lower educational attainment (EA) and an
increased risk for depression has been confirmed in various western
countries. This study examines whether pleiotropic genetic effects
contribute to this association. Therefore, data were analyzed from a
total of 9662 major depressive disorder (MDD) cases and 14 949 controls
(with no lifetime MDD diagnosis) from the Psychiatric Genomics
Consortium with additional Dutch and Estonian data. The association of
EA and MDD was assessed with logistic regression in 15 138 individuals
indicating a significantly negative association in our sample with an
odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in
EA. With data of 884 105 autosomal common single-nucleotide
polymorphisms (SNPs), three methods were applied to test for pleiotropy
between MDD and EA: (i) genetic profile risk scores (GPRS) derived from
training data for EA (independent meta-analysis on similar to 120 000
subjects) and MDD (using a 10-fold leave-one-out procedure in the
current sample), (ii) bivariate genomic-relationship-matrix restricted
maximum likelihood (GREML) and (iii) SNP effect concordance analysis
(SECA). With these methods, we found (i) that the EA-GPRS did not
predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak
negative genetic correlation with bivariate GREML analyses, but this
correlation was not consistently significant, (iii) no evidence for
concordance of MDD and EA SNP effects with SECA analysis. To conclude,
our study confirms an association of lower EA and MDD risk, but this
association was not because of measurable pleiotropic genetic effects,
which suggests that environmental factors could be involved, for
example, socioeconomic status.
