Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland: Scottish Family Health Study (GS:SFHS)

Ana Maria Fernandez-Pujals (Lead / Corresponding author), Mark James Adams, Pippa Thomson, Andrew G. McKechanie, Douglas H. R. Blackwood, Blair H. Smith, Anna F. Dominiczak, Andrew D. Morris, Keith Matthews, Archie Campbell, Pamela Linksted, Chris S. Haley, Ian J. Deary, David J. Porteous, Donald J. MacIntyre, Andrew M. McIntosh

Research output: Contribution to journalArticle

38 Citations (Scopus)
270 Downloads (Pure)

Abstract

The heritability of Major Depressive Disorder (MDD) has been estimated at 37% based largely on twin studies that rely on contested assumptions. More recently, the heritability of MDD has been estimated on large populations from registries such as the Swedish, Finnish, and Chinese cohorts. Family-based designs utilise a number of different relationships and provide an alternative means of estimating heritability. Generation Scotland: Scottish Family Health Study (GS:SFHS) is a large (n = 20,198), family-based population study designed to identify the genetic determinants of common diseases, including Major Depressive Disorder. Two thousand seven hundred and six individuals were SCID diagnosed with MDD, 13.5% of the cohort, from which we inferred a population prevalence of 12.2% (95% credible interval: 11.4% to 13.1%). Increased risk of MDD was associated with being female, unemployed due to a disability, current smokers, former drinkers, and living in areas of greater social deprivation. The heritability of MDD in GS:SFHS was between 28% and 44%, estimated from a pedigree model. The genetic correlation of MDD between sexes, age of onset, and illness course were examined and showed strong genetic correlations. The genetic correlation between males and females with MDD was 0.75 (0.43 to 0.99); between earlier (≤ age 40) and later (> age 40) onset was 0.85 (0.66 to 0.98); and between single and recurrent episodic illness course was 0.87 (0.72 to 0.98). We found that the heritability of recurrent MDD illness course was significantly greater than the heritability of single MDD illness course. The study confirms a moderate genetic contribution to depression, with a small contribution of the common family environment (variance proportion = 0.07, CI: 0.01 to 0.15), and supports the relationship of MDD with previously identified risk factors. This study did not find robust support for genetic differences in MDD due to sex, age of onset, or illness course. However, we found an intriguing difference in heritability between recurrent and single MDD illness course. These findings establish GS:SFHS as a valuable cohort for the genetic investigation of MDD.

Original languageEnglish
Article numbere0142197
Number of pages18
JournalPLoS ONE
Volume10
Issue number11
DOIs
Publication statusPublished - 16 Nov 2015

Fingerprint Dive into the research topics of 'Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland: Scottish Family Health Study (GS:SFHS)'. Together they form a unique fingerprint.

  • Profiles

    No photo of Keith Matthews

    Matthews, Keith

    Person: Academic

    Cite this

    Fernandez-Pujals, A. M., Adams, M. J., Thomson, P., McKechanie, A. G., Blackwood, D. H. R., Smith, B. H., Dominiczak, A. F., Morris, A. D., Matthews, K., Campbell, A., Linksted, P., Haley, C. S., Deary, I. J., Porteous, D. J., MacIntyre, D. J., & McIntosh, A. M. (2015). Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland: Scottish Family Health Study (GS:SFHS). PLoS ONE, 10(11), [e0142197]. https://doi.org/10.1371/journal.pone.0142197