Quantifying between-cohort and between-sex genetic heterogeneity in major depressive disorder

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Publisher: Wiley Subscription Services, Inc.
Document Type: Report
Length: 329 words

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Byline: Maciej Trzaskowski, Divya Mehta, Wouter J. Peyrot, David Hawkes, Daniel Davies,David M. Howard, Kathryn E. Kemper, Julia Sidorenko, Robert Maier, Stephan Ripke, Manuel Mattheisen, Bernhard T. Baune, Hans J. Grabe, Andrew C. Heath, Lisa Jones, Ian Jones, Pamela A.F. Madden, Andrew M. McIntosh, Gerome Breen, Cathryn M. Lewis, Anders D. Borglum, Patrick F. Sullivan,Nicholas G. Martin,Kenneth S. Kendler, Douglas F. Levinson,Naomi R. Wray, Keywords: depression; genetic heterogeneity; LD score regression; MDD; sex differences Major depressive disorder (MDD) is clinically heterogeneous with prevalence rates twice as high in women as in men. There are many possible sources of heterogeneity in MDD most of which are not measured in a sufficiently comparable way across study samples. Here, we assess genetic heterogeneity based on two fundamental measures, between-cohort and between-sex heterogeneity. First, we used genome-wide association study (GWAS) summary statistics to investigate between-cohort genetic heterogeneity using the 29 research cohorts of the Psychiatric Genomics Consortium (PGC; N cases=16,823, N controls=25,632) and found that some of the cohort heterogeneity can be attributed to ascertainment differences (such as recruitment of cases from hospital vs. community sources). Second, we evaluated between-sex genetic heterogeneity using GWAS summary statistics from the PGC, Kaiser Permanente GERA, UK Biobank, and the Danish iPSYCH studies but did not find convincing evidence for genetic differences between the sexes. We conclude that there is no evidence that the heterogeneity between MDD data sets and between sexes reflects genetic heterogeneity. Larger sample sizes with detailed phenotypic records and genomic data remain the key to overcome heterogeneity inherent in assessment of MDD. Article Note: Funding information National Health & Medical Research Council, Award Numbers: 1087889, 1113400, 1078901 CAPTION(S): Supplementary Table S1 Description of PGC29 samples Supplementary Table S2: Bivariate LDSC output for all pairs of two sex by five data sets Supplementary Table S3: Sex-specific SNP-heritabilities and rg Supplementary Table S4: Beta coefficients from 500 sampling analyses used in plotting Figure [Figure 1. Cohort deviation estimates from the linear regression of hSNP2 ...]

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Gale Document Number: GALE|A595164776