Depression Genetics as a Window Into Physical and Mental Health.
Depression Genetics as a Window Into Physical and Mental Health.
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DOI：
10.1016/j.biopsych.2022.09.027
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发表时间：
2022-12-15
影响因子：
10.6
通讯作者：
中科院分区：
文献类型：
--
作者：
预防抑郁症及其伴随的健康问题对于促进健康老龄化和延长寿命至关重要。众所周知，抑郁症和健康状况不佳是相互交织的（1），但为什么仍然是一个积极的调查领域。抑郁症可能与其他健康状况共享潜在的生物学（包括共同的遗传机制）的想法很有吸引力，因为对这些机制的了解可以为改善两者的治疗提供信息。为此，我们年复一年地学习更多关于抑郁症复杂的遗传结构，这在理论上为我们提供了越来越强大的全基因组工具来研究抑郁症与健康之间的关系。到目前为止，这些工具提供了一个有价值的，但相对集中的观点抑郁症的共同遗传风险与特定的合并症，如心血管疾病。另一方面，抑郁症潜在的遗传学被认为是高度多效性的（即与许多特征相关），因此可以为更广泛的精神和身体疾病提供一个窗口，尽管这仍有待充分表征。在这个问题上，Fang和同事（3）报告了迄今为止规模最大，最有力的检查结果之一，即抑郁症的遗传易感性如何与广泛的身心健康状况相关，在密歇根基因组计划的真实世界电子健康记录（EHR）中进行了一项全表型关联研究（PheWAS），这是一个医院嵌入式生物库，000名欧洲血统的无关参与者。与全基因组关联研究（GWAS）不同，该研究测试了数百万种常见遗传变异与单个感兴趣表型之间的关联，PheWAS采用相反的方法，评估了单个感兴趣暴露与许多表型的关系（4）。虽然最初的PheWAS工作集中在特定的遗传变异作为暴露（4），使用多基因评分的PheWAS-它汇总了基因组中许多变异的风险影响-准备将GWAS关于复杂精神疾病的见解带回临床研究环境（图1）。考虑到它们在常规患者护理中的使用，医院EHR自然地捕获广泛的临床表型以用于评估多效性和共享风险，否则组装可能具有挑战性。[图1]
Preventing depression and its concomitant health issues is critical to promote healthy aging and extend lifespan. It is well known that depression and poor health are intertwined (1), but why remains an area of active inquiry. The idea that depression may share underlying biology—including common genetic mechanisms—with other health conditions is appealing, as knowledge of such mechanisms could inform treatments to ameliorate both. To that end, we are learning year upon year more about the complex genetic architecture of major depression (2), which provides us in theory with increasingly powerful genome-wide tools to study the relationship between depression and health. Thus far such tools have offered a valuable but relatively focused view of depression’s shared genetic risk with specific comorbidities, such as cardiovascular disease. On the other hand, the genetics underlying depression are expected to be highly pleiotropic (ie, associated with many traits) and could thus provide a window into a much broader spectrum of mental and physical illnesses—though this remains to be fully characterized. In this issue, Fang and colleagues (3) report results from one of the largest and most well-powered examinations to date of how genetic liability for depression relates to a wide range of physical and mental health conditions, conducting a phenome-wide association study (PheWAS) in real-world electronic health records (EHRs) from the Michigan Genomics Initiative, a hospital-embedded biobank with over 46,000 unrelated participants of European ancestry. Unlike the genome-wide association study (GWAS), which tests the associations between millions of common genetic variants and a single phenotype of interest, a PheWAS takes the reverse approach, where a single exposure of interest is assessed for its relationship to many phenotypes (4). While initial PheWAS efforts focused on specific genetic variants as an exposure (4), a PheWAS using polygenic scores—which aggregate the risk effects of many variants across the genome—is poised to take GWAS insights about complex psychiatric disorders back into the clinical research setting (Figure 1). Given their use in routine patient care, hospital EHRs naturally capture a broad range of clinical phenotypes for assessing pleiotropy and shared risk, which can be otherwise challenging to assemble.[FIGURE 1]
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DOI：
10.1146/annurev-genom-090314-024956
发表时间：
2016-08-31
影响因子：
8.7
作者：
Denny JC;Bastarache L;Roden DM
通讯作者：
Roden DM
影响因子：
11
作者：
Dennis, Jessica;Sealock, Julia;Davis, Lea K.
通讯作者：
Davis, Lea K.
影响因子：
30.8
作者：
Werme, Josefin;van der Sluis, Sophie;de Leeuw, Christiaan A.
通讯作者：
de Leeuw, Christiaan A.
影响因子：
6.8
作者：
McCoy TH;Castro VM;Snapper L;Hart K;Januzzi JL;Huffman JC;Perlis RH
通讯作者：
Perlis RH
影响因子：
10.6
作者：
Fang, Yu;Fritsche, Lars G.;Richmond-Rakerd, Leah S.
通讯作者：
Richmond-Rakerd, Leah S.