Department of Psychiatry (Guintivano, Bauer, Watson, Krohn, Rubinow, Meltzer-Brody, Sullivan), Department of Genetics (Raffield, Li, Sullivan), and Department of Biostatistics (Li), University of North Carolina at Chapel Hill; Child Health Research Centre (Byrne, Kiewa), Institute for Molecular Bioscience (Byrne, Walker), Frazer Institute (Olsen), School of Public Health (Whiteman), and Queensland Brain Institute (Wray), University of Queensland, Brisbane, Australia; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm (Yao, Lu, Xiong, Viktorin, Sullivan); Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond (Aberg, van den Oord); Division of Psychiatry (Adams, McIntosh), Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer (A. Campbell), and Usher Institute for Population Health Sciences and Informatics (A. Campbell), University of Edinburgh, Edinburgh; MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Institute for Infectious Diseases and Molecular Medicine (M.L. Campbell), SAMRC Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry, and Neuroscience Institute (Koen, Stein), and Department of Paediatrics and Child Health and MRC Unit on Child and Adolescent Health (Zar), University of Cape Town, Cape Town, South Africa; Global Initiative for Neuropsychiatric Genetics Education in Research (M.L. Campbell) and Stanley Center for Psychiatric Research (Sealock), Broad Institute, Cambridge, Mass.; Center for Precision Psychiatry, Department of Psychiatry (Choi, Feng, Smoller), Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine (Choi, Feng, Smoller), and Analytic and Translational Genetics Unit (Sealock), Massachusetts General Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston (Choi, Feng, Smoller); Department of Mental Disorders (Corfield, Reichborn-Kjennerud, Tesli) and Center for Genetic Epidemiology and Mental Health (Havdahl), Norwegian Institute of Public Health, Oslo; Nic Waals Institute, Lovisenberg Diaconal Hospital, Oslo (Corfield, Havdahl); Department of Psychology, PROMENTA Research Center (Havdahl), NORMENT Center (Andreassen), K.G. Jebsen Center for Neurodevelopmental Disorders (Andreassen, Westlye), Institute of Clinical Medicine (Reichborn-Kjennerud), and Department of Psychology (Westlye), University of Oslo, Oslo; Department of Medicine (Hucks, Davis), Division of Genetic Medicine (Hucks, Davis), and Vanderbilt Genetics Institute (Hucks), Vanderbilt University Medical Center, Nashville; National Center for Register-Based Research (Mægbæk, Munk-Olsen) and Department of Economics and Business Economics (Mægbæk), Aarhus University, Aarhus, Denmark; Department of Epidemiology, Biostatistics, and Clinical Research, AP-HP Nord-Université Paris Cité, Paris (Mullaert); UMR 1137 IAME, INSERM, Paris (Mullaert); Department of Psychiatry and Behavioral Sciences (Peterson), Institute for Genomics in Health (Peterson), and Department of Psychiatry and Behavioral Sciences (Bigdeli), SUNY Downstate Health Sciences University, Brooklyn; Centre for Academic Mental Health, Population Health Sciences, Bristol Medical School, and MRC Integrative Epidemiology Unit, University of Bristol, Bristol, U.K. (Sallis); Discipline of Psychology, Curtin University, Perth, Australia (Watson); Division of Paediatrics, University of Western Australia, Perth (Watson); Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Yang, Anney, Hubbard, I. Jones, Pardiñas, Di Florio); Psychological Medicine, University of Worcester, Worcester, U.K. (Gordon-Smith, L.A. Jones, Perry); Department of Psychiatry, Catharina Hospital, Eindhoven, the Netherlands (Mihaescu); Department of Health Science and Technology, Aalborg University, Aalborg, Denmark (Nyegaard); Department of Clinical Sciences, Sulaiman AlRajhi University, Bukairiyah, Saudi Arabia (Saquib); Department of Epidemiology, Herbert Wertheim School of Public Health and Human Longevity Science, University of California, San Diego, La Jolla (Shadyab); Division of Mental Health and Addiction (Andreassen), Center for Research and Education in Forensic Psychiatry, Department of Mental Health and Addiction (Tesli), and NORMENT, Division for Mental Health and Addiction (Westlye), Oslo University Hospital, Oslo; Research Service, VA New York Harbor Healthcare System, New York (Bigdeli); Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto (Dennis); INSERM U1266, Université de Paris, Paris (Dubertret); Department of Psychiatry, AP-HP, Louis Mourier Hospital, Colombes, France (Dubertret, Tebeka); Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario (Frey, Van Lieshout); Women's Health Concerns Clinic, St. Joseph's Healthcare Hamilton, Hamilton, Canada (Frey); Department of Psychiatry, Sunnybrook Health Science Centre and Research Institute, Toronto (Grigoriadis); Department of Psychiatry, University of Toronto, Toronto (Grigoriadis, Kennedy, Vigod); Hôpital Bichat, Department of Epidemiology, Biostatistics, and Clinical Research, AP-HP, Paris (Gloaguen); Molecular Brain Science Department, Centre for Addiction and Mental Health, Toronto (Kennedy); Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden (Kunovac Kallak, Skalkidou); Genetic Epidemiology (Martin) and Population Health Program (Olsen, Whiteman), QIMR Berghofer Medical Research Institute, Brisbane, Australia; Parent-Infant Research Institute, Heidelberg Heights, Australia (Milgrom); University of Melbourne, Melbourne, Australia (Milgrom); Department of Clinical Research, Psychiatric Research Unit, University of Southern Denmark, Odense (Munk-Olsen); BC Children's Hospital, Vancouver (Oberlander); Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver (Oberlander); Université Paris Cité, Institute of Psychiatry and Neuroscience of Paris (IPNP), INSERM UMR1266, Team "Genetic vulnerability to addictive and psychiatric disorders," Paris (Ramoz); GHU Paris Psychiatrie et Neurosciences, CMME, Hôpital Sainte-Anne, Paris (Ramoz); Behavioral Sciences and Social Medicine, Florida State University, Daytona Beach (Robertson Blackmore); Department of Psychiatry, University of Wisconsin, Madison (Stowe); Department of Psychiatry, University of Calgary, Calgary, Canada (Taylor); INSERM U1266, Université Paris Cité, Paris (Tebeka); Department of Psychiatry, Women's College Hospital, Toronto (Vigod); Institute of Biological Psychiatry, Mental Health Services, Copenhagen University Hospital, Copenhagen (Werge); Department of Clinical Medicine and LF Center for Geogenetics, Globe Institute, University of Copenhagen, Copenhagen (Werge); iPSYCH, Lundbeck Foundation Initiative for Integrative Psychiatric Research, Copenhagen (Werge).
Am J Psychiatry. 2023 Dec 1;180(12):884-895. doi: 10.1176/appi.ajp.20230053. Epub 2023 Oct 18.
Postpartum depression (PPD) is a common subtype of major depressive disorder (MDD) that is more heritable, yet is understudied in psychiatric genetics. The authors conducted meta-analyses of genome-wide association studies (GWASs) to investigate the genetic architecture of PPD.
Meta-analyses were conducted on 18 cohorts of European ancestry (17,339 PPD cases and 53,426 controls), one cohort of East Asian ancestry (975 cases and 3,780 controls), and one cohort of African ancestry (456 cases and 1,255 controls), totaling 18,770 PPD cases and 58,461 controls. Post-GWAS analyses included 1) single-nucleotide polymorphism (SNP)-based heritability ([Formula: see text]), 2) genetic correlations between PPD and other phenotypes, and 3) enrichment of the PPD GWAS findings in 27 human tissues and 265 cell types from the mouse central and peripheral nervous system.
No SNP achieved genome-wide significance in the European or the trans-ancestry meta-analyses. The [Formula: see text] of PPD was 0.14 (SE=0.02). Significant genetic correlations were estimated for PPD with MDD, bipolar disorder, anxiety disorders, posttraumatic stress disorder, insomnia, age at menarche, and polycystic ovary syndrome. Cell-type enrichment analyses implicate inhibitory neurons in the thalamus and cholinergic neurons within septal nuclei of the hypothalamus, a pattern that differs from MDD.
While more samples are needed to reach genome-wide levels of significance, the results presented confirm PPD as a polygenic and heritable phenotype. There is also evidence that despite a high correlation with MDD, PPD may have unique genetic components. Cell enrichment results suggest GABAergic neurons, which converge on a common mechanism with the only medication approved by the U.S. Food and Drug Administration for PPD (brexanolone).
产后抑郁症（PPD）是一种常见的重性抑郁障碍（MDD）亚型，其遗传性更强，但在精神遗传学研究中却较少被研究。作者对全基因组关联研究（GWAS）进行了荟萃分析，以探讨 PPD 的遗传结构。
对 18 个欧洲血统队列（17339 例 PPD 病例和 53426 例对照）、1 个东亚血统队列（975 例病例和 3780 例对照）和 1 个非洲血统队列（456 例病例和 1255 例对照）进行了荟萃分析，总共有 18770 例 PPD 病例和 58461 例对照。GWAS 后分析包括 1）基于单核苷酸多态性（SNP）的遗传度 ([Formula: see text])，2）PPD 与其他表型之间的遗传相关性，3）在来自小鼠中枢和外周神经系统的 27 个人类组织和 265 种细胞类型中对 PPD GWAS 结果进行富集。
在欧洲或跨血统荟萃分析中，没有 SNP 达到全基因组显著水平。PPD 的遗传度为 0.14（SE=0.02）。PPD 与 MDD、双相情感障碍、焦虑障碍、创伤后应激障碍、失眠、初潮年龄和多囊卵巢综合征之间存在显著的遗传相关性。细胞类型富集分析提示丘脑的抑制性神经元和下丘脑隔核的胆碱能神经元，这一模式与 MDD 不同。
虽然需要更多的样本才能达到全基因组水平的显著性，但目前的结果证实 PPD 是一种多基因遗传的表型。也有证据表明，尽管与 MDD 相关性很高，但 PPD 可能具有独特的遗传成分。细胞富集结果提示 GABA 能神经元，与美国食品和药物管理局唯一批准用于 PPD（brexanolone）的药物有共同的作用机制。
