Genetic analysis identifies molecular systems and biological pathways associated with household income

Hill, W. D.; Davies, N. M.; Ritchie, S. J.; Skene, N. G.; Bryois, J.; Bell, S.; Di Angelantonio, E.; Roberts, D. J.; Xueyi, S.; Davies, G.; Liewald, D. C. M.; Porteous, D. J.; Hayward, C.; Butterworth, A. S.; McIntosh, A. M.; Gale, C. R.; Deary, I. J.

doi:10.1101/573691

bioRxiv · 10.1101/573691

Genetic analysis identifies molecular systems and biological pathways associated with household income

Hill, W. D.·Davies, N. M.·Ritchie, S. J.·Skene, N. G.·Bryois, J.·Bell, S.·Di Angelantonio, E.·Roberts, D. J.·Xueyi, S.·Davies, G.·Liewald, D. C. M.·Porteous, D. J.·Hayward, C.·Butterworth, A. S.·McIntosh, A. M.·Gale, C. R.·Deary, I. J.

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Abstract

Socio-economic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. Previous genome-wide association studies (GWAS) using household income as a marker of SEP have shown that common genetic variants account for 11% of its variation. Here, in a sample of 286,301 participants from UK Biobank, we identified 30 independent genome-wide significant loci, 29 novel, that are associated with household income. Using a recently-developed method to meta-analyze data that leverages power from genetically-correlated traits, we identified an additional 120 income-associated loci. These loci showed clear evidence of functional enrichment, with transcriptional differences identified across multiple cortical tissues, in addition to links with GABAergic and serotonergic neurotransmission. We identified neurogenesis and the components of the synapse as candidate biological systems that are linked with income. By combining our GWAS on income with data from eQTL studies and chromatin interactions, 24 genes were prioritized for follow up, 18 of which were previously associated with cognitive ability. Using Mendelian Randomization, we identified cognitive ability as one of the causal, partly-heritable phenotypes that bridges the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. Significant differences between genetic correlations indicated that, the genetic variants associated with income are related to better mental health than those linked to educational attainment (another commonly-used marker of SEP). Finally, we were able to predict 2.5% of income differences using genetic data alone in an independent sample. These results are important for understanding the observed socioeconomic inequalities in Great Britain today.

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Hill, W. D., Davies, N. M., Ritchie, S. J., Skene, N. G., Bryois, J., Bell, S., Di Angelantonio, E., Roberts, D. J., Xueyi, S., Davies, G., Liewald, D. C. M., Porteous, D. J., Hayward, C., Butterworth, A. S., McIntosh, A. M., Gale, C. R., Deary, I. J.. 2019-03-12. Genetic analysis identifies molecular systems and biological pathways associated with household income. https://doi.org/10.1101/573691

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