University of Dundee Epidemiology and heritability of Major Depressive Disorder, stratified by age of onset, sex, and illness course in Generation Scotland Fernandez-Pujals,

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 PLOS ONE | DOI:10.1371/journal.pone.0142197 November 16, 2015 1 / 18 OPEN ACCESS Citation: Fernandez-Pujals AM, Adams MJ, Thomson P, McKechanie AG, Blackwood DHR, Smith BH, et al. (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. doi:10.1371/journal. pone.0142197 Editor: Klaus Ebmeier, University of Oxford, UNITED KINGDOM Received: March 19, 2015 Accepted: October 18, 2015 Published: November 16, 2015 Copyright: © 2015 Fernandez-Pujals et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: Data are available from the Generation Scotland Access Committee for researchers who meet the criteria for access to confidential data. Information about requesting access to the data for researchers can be found at the Generation Scotland website: www. generationscotland.org. The ethical consent granted by the participants in the study requires the privacy of the individuals to be ensured, and the individual ethical approval of each study upon application to the 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.