Nausea and vomiting in pregnancy (NVP) affects ~70% of pregnant women to different degrees. Historically, the dominant aetiological theory of these conditions was psychogenic in origin, being commonly described as a conversion... [ view full abstract ]
Nausea and vomiting in pregnancy (NVP) affects ~70% of pregnant women to different degrees. Historically, the dominant aetiological theory of these conditions was psychogenic in origin, being commonly described as a conversion disorder. Recent studies have shown that women who experience severe NVP have higher rates of major depressive disorder (MDD) prior to the index pregnancy. NVP and depression are significantly heritable. We therefore hypothesize that there is a genetic correlation between NVP and depression.
We first carried out a genomewide association study (GWAS) meta-analysis on the presence of NVP with the summary statistics provided by two samples which are part of the NVP Genetics Consortium: QIMR Berghofer Medical Research Institute (n = 1441) and the Avon Longitudinal Study of Parents and Children (n = 7053). The GWAS analyses included age and age squared at time of interview, singleton/twin pregnancy variables, and the first four ancestry principal components as covariates. Both autosomal and X chromosomes were analysed and genotypes were analysed as allele doses. Meta-analysis of summary statistics of the two samples was carried out with METAL simultaneously. We conducted a linkage disequilibrium score regression with the PGC-MDD results to calculate the genetic correlation of both traits using SECA (SNP effect concordance analysis using genome-wide association summary results, Nyholt 2014).
The GWAS meta-analysis did not show any genome-wide significant hit. The SNP with the lowest p-value (rs2238144, p = 1.237e-07) is located within the RAPGEF3 gene (Rap guanine nucleotide exchange Factor GEF 3) in a DNAse hypersensitivity region on chromosome 12, with signalling pathway participating in the stimulation of the placental cell fusion.
There was a significant concordance of genetic risk between NVP and MDD, with allelic effects that increase risk for both traits.
'The implications of these results for the treatment of depression and anxiety with severe NVP will be discussed.
Nyholt D.R. (2014). SECA: SNP effect concordance analysis using genome-wide association summary results. Bioinformatics 30, 2086-2088
Psychopathology (e.g., Internalizing, Externalizing, Psychosis) , Other
