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Sex differences in the genetic architecture of depression.

Scientific reports | 2020

The prevalence and clinical characteristics of depressive disorders differ between women and men; however, the genetic contribution to sex differences in depressive disorders has not been elucidated. To evaluate sex-specific differences in the genetic architecture of depression, whole exome sequencing of samples from 1000 patients (70.7% female) with depressive disorder was conducted. Control data from healthy individuals with no psychiatric disorder (n = 72, 26.4% female) and East-Asian subpopulation 1000 Genome Project data (n = 207, 50.7% female) were included. The genetic variation between men and women was directly compared using both qualitative and quantitative research designs. Qualitative analysis identified five genetic markers potentially associated with increased risk of depressive disorder in females, including three variants (rs201432982 within PDE4A, and rs62640397 and rs79442975 within FDX1L) mapping to chromosome 19p13.2 and two novel variants (rs820182 and rs820148) within MYO15B at the chromosome 17p25.1 locus. Depressed patients homozygous for these variants showed more severe depressive symptoms and higher suicidality than those who were not homozygotes (i.e., heterozygotes and homozygotes for the non-associated allele). Quantitative analysis demonstrated that the genetic burden of protein-truncating and deleterious variants was higher in males than females, even after permutation testing. Our study provides novel genetic evidence that the higher prevalence of depressive disorders in women may be attributable to inherited variants.

Pubmed ID: 32555505 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


R Project for Statistical Computing (tool)

RRID:SCR_001905

Software environment and programming language for statistical computing and graphics. R is integrated suite of software facilities for data manipulation, calculation and graphical display. Can be extended via packages. Some packages are supplied with the R distribution and more are available through CRAN family.It compiles and runs on wide variety of UNIX platforms, Windows and MacOS.

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1000 Genomes Project and AWS (tool)

RRID:SCR_008801

A dataset containing the full genomic sequence of 1,700 individuals, freely available for research use. The 1000 Genomes Project is an international research effort coordinated by a consortium of 75 companies and organizations to establish the most detailed catalogue of human genetic variation. The project has grown to 200 terabytes of genomic data including DNA sequenced from more than 1,700 individuals that researchers can now access on AWS for use in disease research free of charge. The dataset containing the full genomic sequence of 1,700 individuals is now available to all via Amazon S3. The data can be found at: http://s3.amazonaws.com/1000genomes The 1000 Genomes Project aims to include the genomes of more than 2,662 individuals from 26 populations around the world, and the NIH will continue to add the remaining genome samples to the data collection this year. Public Data Sets on AWS provide a centralized repository of public data hosted on Amazon Simple Storage Service (Amazon S3). The data can be seamlessly accessed from AWS services such Amazon Elastic Compute Cloud (Amazon EC2) and Amazon Elastic MapReduce (Amazon EMR), which provide organizations with the highly scalable compute resources needed to take advantage of these large data collections. AWS is storing the public data sets at no charge to the community. Researchers pay only for the additional AWS resources they need for further processing or analysis of the data. All 200 TB of the latest 1000 Genomes Project data is available in a publicly available Amazon S3 bucket. You can access the data via simple HTTP requests, or take advantage of the AWS SDKs in languages such as Ruby, Java, Python, .NET and PHP. Researchers can use the Amazon EC2 utility computing service to dive into this data without the usual capital investment required to work with data at this scale. AWS also provides a number of orchestration and automation services to help teams make their research available to others to remix and reuse. Making the data available via a bucket in Amazon S3 also means that customers can crunch the information using Hadoop via Amazon Elastic MapReduce, and take advantage of the growing collection of tools for running bioinformatics job flows, such as CloudBurst and Crossbow.

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FISHER (tool)

RRID:SCR_009181

THIS RESOURCE IS NO LONGER IN SERVICE, documented on February 1st, 2022. Software application for genetic analysis of classical biometric traits like blood pressure or height that are caused by a combination of polygenic inheritance and complex environmental forces. (entry from Genetic Analysis Software)

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SIFT (tool)

RRID:SCR_012813

Data analysis service to predict whether an amino acid substitution affects protein function based on sequence homology and the physical properties of amino acids. SIFT can be applied to naturally occurring nonsynonymous polymorphisms and laboratory-induced missense mutations. (entry from Genetic Analysis Software) Web service is also available.

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