Genetics of depressive symptoms in adolescence

Hannah Sallis,Lavinia Paternoster,Albertine J Oldehinkel,George Davey Smith,Jonathan Evans,Eva Krapohl,Robyn Wootton

doi:10.1186/s12888-017-1484-y

Abstract

BackgroundDespite many attempts to understand the genetic architecture of depression, little progress has been made. The majority of these studies, however, have been carried out in adults and do not account for the potential influence of development.MethodsThe Avon Longitudinal Study of Parents and Children (ALSPAC) is a longitudinal pregnancy cohort which recruited participants between April 1991 and December 1992. Analyses were replicated in two independent European cohorts. Genome-wide complex trait analysis (GCTA) software was used to investigate SNP-heritability (h2SNP) of depression across adolescence, the role of puberty was investigated by stratifying these estimates according to pubertal onset. Genome-wide association studies were performed to identify genetic variants associated with depression at different stages of development.ResultsHeritability was estimated between the ages of 11 and 18 with sample sizes ranging from 3289 to 5480. Heritability was low with an apparent peak was found at age 13 (h2 = 0.17, p = 0.006). Confidence intervals around these estimates suggest an upper-bound to h2SNP of around 30%. A variant located on chromosome 7 was found to be associated with depressive symptoms at age 13 in ALSPAC (rs138191010: β = 0.142, p = 2.51 × 10−8), although this was not replicated.ConclusionsAlthough power is a potential limitation, the observed patterns provide interesting hypotheses surrounding the heritability of depression at different developmental stages. We found substantially lower estimates for depressive symptoms at age 11 (0.07) compared to those previously estimated in adults (0.21). We also found a peak in heritability at age 13. These findings suggest environmental factors are likely to be more important in the aetiology of depressive symptoms in early adolescence than in adulthood.

Highlights

Despite many attempts to understand the genetic architecture of depression, little progress has been made
The Psychiatric Genomics Consortium (PGC) recently identified 108 risk loci for schizophrenia [1], whereas corresponding analyses performed for major depressive disorder (MDD) failed to find any robustly associated loci [2]
A meta-analysis of twin studies estimated the heritability of MDD in adults to be 0.37 [9], while recent work by the PGC used SNP-based methods implemented by the Genome-wide Complex Trait Analysis (GCTA) software [10] to estimate a common SNPheritability (h2SNP) of 0.21 [11]

Summary

Introduction

Despite many attempts to understand the genetic architecture of depression, little progress has been made. A meta-analysis of twin studies estimated the heritability of MDD in adults to be 0.37 (95% CI: 0.31, 0.42) [9], while recent work by the PGC used SNP-based methods implemented by the Genome-wide Complex Trait Analysis (GCTA) software [10] to estimate a common SNPheritability (h2SNP) of 0.21 [11]. These estimates may at first appear inconsistent, the estimate from twin studies is expected to be higher as they take into account variation across the entire genome, whereas h2SNP estimates incorporate only common variants captured by SNPs included on genotyping platforms

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