Epigenetic prediction of major depressive disorder.
Epigenetic prediction of major depressive disorder.
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DOI：
10.1038/s41380-020-0808-3
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发表时间：
2021-09
影响因子：
11
通讯作者：
McIntosh AM
中科院分区：
文献类型：
--
作者：
Barbu MC;Shen X;Walker RM;Howard DM;Evans KL;Whalley HC;Porteous DJ;Morris SW;Deary IJ;Zeng Y;Marioni RE;Clarke TK;McIntosh AM
DNA甲基化（DNAm）的变化与吸烟和体重指数（BMI）等生活方式因素有关，但很少有研究探索其识别重度抑郁症（MDD）个体的能力。使用全基因组CpG甲基化的惩罚回归，我们测试了在1223例MDD病例和1824例对照中训练的DNAm风险评分（MRS）是否可以在独立样本中区分病例（n = 363）和对照（n = 1417），并将其预测准确性与多基因风险评分（PRS）进行比较。MRS解释了MDD变异的1.75%（β = 0.338，p = 1.17 × 10−7），在调整生活方式因素后仍相关（β = 0.219，p = 0.001，R2 = 0.68%）。当与PRS（β = 0.384，p = 4.69 × 10−9）一起建模时，MRS仍然与MDD（β = 0.327，p = 5.66 × 10−7）相关。MRS还与招募时表现良好但在后期评估时继续发展为MDD的MDD事件病例相关（β = 0.193，p = 0.016，R2 = 0.52%）。遗传力分析发现，加性遗传效应解释了MRS中22%的方差，另外19%由家系相关遗传效应解释，16%由共享的夫妇环境解释。吸烟状态也与MRS密切相关（β = 0.440，p ≤ 2 × 10−16）。从训练集中去除吸烟者后，MRS与BMI密切相关（β = 0.053，p = 0.021）。我们测试了MRS与61种行为表型的相关性，发现虽然PRS与心理社会和精神健康表型相关，但MRS与生活方式和社会人口因素相关性更强。基于DNAm的MDD风险评分显著区分MDD病例和独立数据集中的对照，并可能代表与MDD预测相关的生活方式因素暴露的档案。
Variation in DNA methylation (DNAm) is associated with lifestyle factors such as smoking and body mass index (BMI) but there has been little research exploring its ability to identify individuals with major depressive disorder (MDD). Using penalised regression on genome-wide CpG methylation, we tested whether DNAm risk scores (MRS), trained on 1223 MDD cases and 1824 controls, could discriminate between cases (n = 363) and controls (n = 1417) in an independent sample, comparing their predictive accuracy to polygenic risk scores (PRS). The MRS explained 1.75% of the variance in MDD (β = 0.338, p = 1.17 × 10−7) and remained associated after adjustment for lifestyle factors (β = 0.219, p = 0.001, R2 = 0.68%). When modelled alongside PRS (β = 0.384, p = 4.69 × 10−9) the MRS remained associated with MDD (β = 0.327, p = 5.66 × 10−7). The MRS was also associated with incident cases of MDD who were well at recruitment but went on to develop MDD at a later assessment (β = 0.193, p = 0.016, R2 = 0.52%). Heritability analyses found additive genetic effects explained 22% of variance in the MRS, with a further 19% explained by pedigree-associated genetic effects and 16% by the shared couple environment. Smoking status was also strongly associated with MRS (β = 0.440, p ≤ 2 × 10−16). After removing smokers from the training set, the MRS strongly associated with BMI (β = 0.053, p = 0.021). We tested the association of MRS with 61 behavioural phenotypes and found that whilst PRS were associated with psychosocial and mental health phenotypes, MRS were more strongly associated with lifestyle and sociodemographic factors. DNAm-based risk scores of MDD significantly discriminated MDD cases from controls in an independent dataset and may represent an archive of exposures to lifestyle factors that are relevant to the prediction of MDD.
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影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
3.7
作者：
Opel, Nils;Redlich, Ronny;Dannlowski, Udo
通讯作者：
Dannlowski, Udo
影响因子：
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作者：
Fortin, Jean-Philippe;Fertig, Elana;Hansen, Kasper
通讯作者：
Hansen, Kasper
影响因子：
12.3
作者：
Gaunt TR;Shihab HA;Hemani G;Min JL;Woodward G;Lyttleton O;Zheng J;Duggirala A;McArdle WL;Ho K;Ring SM;Evans DM;Davey Smith G;Relton CL
通讯作者：
Relton CL
影响因子：
7.2
作者：
Hafferty JD;Campbell AI;Navrady LB;Adams MJ;MacIntyre D;Lawrie SM;Nicodemus K;Porteous DJ;McIntosh AM
通讯作者：
McIntosh AM