Genetic heterogeneity and subtypes of major depression.
Genetic heterogeneity and subtypes of major depression.
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遗传异质性和严重抑郁症的亚型。
DOI：
10.1038/s41380-021-01413-6
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发表时间：
2022-03
影响因子：
11
通讯作者：
Lu, Yi
中科院分区：
文献类型：
--
作者：
Thuy-Dung Nguyen;Harder, Arvid;Xiong, Ying;Kowalec, Kaarina;Hagg, Sara;Cai, Na;Kuja-Halkola, Ralf;Dalman, Christina;Sullivan, Patrick F.;Lu, Yi
重度抑郁症(MD)是一种异质性疾病；然而，遗传因素在多大程度上区分MD患者亚群(遗传异质性)仍不确定。这项研究寻找MD遗传异质性的证据。采用UK Biobank队列，在8个对照组中定义了16个MD亚型(植物症状、症状严重程度、共患焦虑症、起病年龄、复发、自杀、损害和产后抑郁症；N~3000~47000)。为了比较这些亚型的遗传成分，进行了亚型特有的全基因组关联研究，以估计SNP的遗传力，以及亚型比较中的遗传相关性以及与其他相关疾病或性状的相关性。结果表明，MD亚型的SNP遗传度和遗传相关性在亚型比较和与其他相关疾病/性状方面存在差异。三个亚型比较(植物症状、发病年龄和损害)在SNP遗传率上有显著差异；而亚型比较中的遗传相关性在0.55到0.86之间，这表明MD亚型之间的遗传图谱只有部分共享。此外，临床上更具挑战性的亚型，例如早发性、复发性、自杀倾向、更严重的损害，与其他精神疾病有更强的遗传相关性。具有不典型样特征的MD与体重指数呈正相关(+0.40)，而无不典型样特征的MD与体重指数呈负相关(−0.09)。发现了具有亚型特异性效应的新的基因组基因座。这些结果为MD内的遗传异质性提供了迄今为止最全面的证据，并表明通过研究具有部分不同病因的亚型可以有效地降低MD的表型复杂性。
Major depression (MD) is a heterogeneous disorder; however, the extent to which genetic factors distinguish MD patient subgroups (genetic heterogeneity) remains uncertain. This study sought evidence for genetic heterogeneity in MD. Using UK Biobank cohort, the authors defined 16 MD subtypes within eight comparison groups (vegetative symptoms, symptom severity, comorbid anxiety disorder, age at onset, recurrence, suicidality, impairment and postpartum depression; N~3 000-47 000). To compare genetic component of these subtypes, subtype-specific genome-wide association studies were performed to estimate SNP-heritability, and genetic correlations within subtype comparison and with other related disorders or traits. The findings indicated that MD subtypes were divergent in their SNP-heritability, and genetic correlations both within subtype comparisons and with other related disorders/traits. Three subtype comparisons (vegetative symptoms, age at onset, and impairment) showed significant differences in SNP-heritability; while genetic correlations within subtypes comparisons ranged from 0.55 to 0.86, suggesting genetic profiles are only partially shared among MD subtypes. Furthermore, subtypes that are more clinically challenging, e.g., early-onset, recurrent, suicidal, more severely impaired, had stronger genetic correlations with other psychiatric disorders. MD with atypical-like features showed a positive genetic correlation (+0.40) with BMI while a negative correlation (−0.09) was found in those without atypical-like features. Novel genomic loci with subtype-specific effects were identified. These results provide the most comprehensive evidence to date for genetic heterogeneity within MD, and suggest that the phenotypic complexity of MD can be effectively reduced by studying the subtypes which share partially distinct etiologies.
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基因发现和多基因预测，从基因组全基因组协会的教育程度研究中，有110万个人。
影响因子：
30.8
作者：
Lee JJ;Wedow R;Okbay A;Kong E;Maghzian O;Zacher M;Nguyen-Viet TA;Bowers P;Sidorenko J;Karlsson Linnér R;Fontana MA;Kundu T;Lee C;Li H;Li R;Royer R;Timshel PN;Walters RK;Willoughby EA;Yengo L;23andMe Research Team;COGENT (Cognitive Genomics Consortium);Social Science Genetic Association Consortium;Alver M;Bao Y;Clark DW;Day FR;Furlotte NA;Joshi PK;Kemper KE;Kleinman A;Langenberg C;Mägi R;Trampush JW;Verma SS;Wu Y;Lam M;Zhao JH;Zheng Z;Boardman JD;Campbell H;Freese J;Harris KM;Hayward C;Herd P;Kumari M;Lencz T;Luan J;Malhotra AK;Metspalu A;Milani L;Ong KK;Perry JRB;Porteous DJ;Ritchie MD;Smart MC;Smith BH;Tung JY;Wareham NJ;Wilson JF;Beauchamp JP;Conley DC;Esko T;Lehrer SF;Magnusson PKE;Oskarsson S;Pers TH;Robinson MR;Thom K;Watson C;Chabris CF;Meyer MN;Laibson DI;Yang J;Johannesson M;Koellinger PD;Turley P;Visscher PM;Benjamin DJ;Cesarini D
通讯作者：
Cesarini D
影响因子：
5
作者：
Fry A;Littlejohns TJ;Sudlow C;Doherty N;Adamska L;Sprosen T;Collins R;Allen NE
通讯作者：
Allen NE
影响因子：
3.5
作者：
Cai N;Choi KW;Fried EI
通讯作者：
Fried EI
影响因子：
30.8
作者：
Bulik-Sullivan, Brendan K.;Loh, Po-Ru;Finucane, Hilary K.;Ripke, Stephan;Yang, Jian;Patterson, Nick;Daly, Mark J.;Price, Alkes L.;Neale, Benjamin M.
通讯作者：
Neale, Benjamin M.
影响因子：
6.9
作者：
Badini I;Coleman JRI;Hagenaars SP;Hotopf M;Breen G;Lewis CM;Fabbri C
通讯作者：
Fabbri C