The American Journal of Human Genetics This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

The shared ancestry between the C9orf72 hexanucleotide repeat expansion and intermediate-length alleles using haplotype sharing trees and HAPTK
Using haplotype sharing trees and majority-based ancestral haplotypes, we demonstrate that the C9orf72 hexanucleotide repeat expansion and alleles with ≥18–20 repeats share large haplotype blocks, indicating very recent shared ancestry. This was in sharp contrast to the shorter alleles, suggesting that expansions might be formed from the longer repeat alleles. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 18, 2024 Category: Genetics & Stem Cells Authors: Osma S. Rautila, Karri Kaivola, Harri Rautila, Laura Hokkanen, Jyrki Launes, Timo E. Strandberg, Hannu Laaksovirta, Johanna Palmio, Pentti J. Tienari Tags: Article Source Type: research

Regulatory features aid interpretation of 3 ′UTR variants
Genetic variants in noncoding regions such as 3 ′ UTRs are associated with disease and phenotypes, but their functional interpretation remains challenging. We have identified specific regulatory elements in 3′ UTRs that are enriched for variants that impact gene expression or phenotype and have developed a tool specifically designed to interp ret 3′ UTR variants. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 17, 2024 Category: Genetics & Stem Cells Authors: Lindsay Romo, Scott D. Findlay, Christopher B. Burge Tags: Article Source Type: research

A common NFKB1 variant detected through antibody analysis in UK Biobank predicts risk of infection and allergy
Infectious agents contribute significantly to the global burden of diseases, through both acute infection and their chronic sequelae. We identified an insertion-deletion variant thought to affect NFKB1 expression as a causal variant —central to serological responses to diverse infectious agents, risk of infection, immune cell survival, antibody production, and inflammation. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 16, 2024 Category: Genetics & Stem Cells Authors: Amanda Y. Chong, Nicole Brenner, Andres Jimenez-Kaufmann, Adrian Cortes, Michael Hill, Thomas J. Littlejohns, James J. Gilchrist, Benjamin P. Fairfax, Julian C. Knight, Flavia Hodel, Jacques Fellay, Gil McVean, Andres Moreno-Estrada, Tim Waterboer, Adrian Tags: Article Source Type: research

Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements
This study uses functional genomics approaches to assess candidate cis-regulatory elements (cCREs) for MAPT in neurons. The study suggests that impactful rare non-coding variants in MAPT cCREs (hypothesized to result in lower tau expression) may be protective against neurodegeneration, emphasizing the potential importance of rare non-coding variants in disease risk. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 16, 2024 Category: Genetics & Stem Cells Authors: Brianne B. Rogers, Ashlyn G. Anderson, Shelby N. Lauzon, M. Natalie Davis, Rebecca M. Hauser, Sydney C. Roberts, Ivan Rodriguez-Nunez, Katie Trausch-Lowther, Erin A. Barinaga, Paige I. Hall, Matthew T. Knuesel, Jared W. Taylor, Mark Mackiewicz, Brian S. R Tags: Article Source Type: research

Adaptation of a mutual exclusivity framework to identify driver mutations within oncogenic pathways
Cancer is known to arise after a cell experiences multiple driver mutations that allow it to grow uncontrollably and ultimately metastasize to distant anatomic sites. In this paper, we introduce a computational approach for identifying driver mutations by leveraging the mutual exclusivity of genes and variants within oncogenic pathways. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 16, 2024 Category: Genetics & Stem Cells Authors: Xinjun Wang, Caroline Kostrzewa, Allison Reiner, Ronglai Shen, Colin Begg Tags: Article Source Type: research

STIGMA: Single-cell tissue-specific gene prioritization using machine learning
Single-cell tissue-specific gene prioritization using machine learning (STIGMA) is an approach to prioritize candidate genes for congenital diseases. STIGMA uses single-cell RNA-seq data to capture the dynamics of gene expression within cell populations across developmental time, making it a powerful tool for the discovery of disease-associated genes. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 15, 2024 Category: Genetics & Stem Cells Authors: Saranya Balachandran, Cesar A. Prada-Medina, Martin A. Mensah, Naseebullah Kakar, Inga Nagel, Jelena Pozojevic, Enrique Audain, Marc-Phillip Hitz, Martin Kircher, Varun K.A. Sreenivasan, Malte Spielmann Tags: Article Source Type: research

A comprehensive analysis of clinical and polygenic germline influences on somatic mutational burden
We investigated how genetic and non-genetic host characteristics influence the accumulation of both somatic point mutations and copy number variants. We found fine-scale genetic ancestry and polygenic risk scores were associated with tumor mutational burden. We additionally found that many of these associations impacted overall survival. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 10, 2024 Category: Genetics & Stem Cells Authors: Kodi Taraszka, Stefan Groha, David King, Robert Tell, Kevin White, Elad Ziv, Noah Zaitlen, Alexander Gusev Tags: Article Source Type: research

Systematic identification of genotype-dependent enhancer variants in eosinophilic esophagitis
This study is an important step toward understanding how EoE genetic r isk variants lead to genotype-dependent biology. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 5, 2024 Category: Genetics & Stem Cells Authors: Molly S. Shook, Xiaoming Lu, Xiaoting Chen, Sreeja Parameswaran, Lee Edsall, Michael P. Trimarchi, Kevin Ernst, Marissa Granitto, Carmy Forney, Omer A. Donmez, Arame A. Diouf, Andrew VonHandorf, Marc E. Rothenberg, Matthew T. Weirauch, Leah C. Kottyan Tags: Article Source Type: research

Genetic determinants of IgG antibody response to COVID-19 vaccination
Antibody production after COVID-19 vaccination is closely related to vaccine efficacy. Our findings about its host genetic determinants provide insights into the biological mechanism of host responses to COVID-19 vaccines and have guiding significance for vaccine design and vaccination. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Shengzhe Bian, Xinxin Guo, Xilai Yang, Yuandan Wei, Zijing Yang, Shiyao Cheng, Jiaqi Yan, Yongkun Chen, Guo-Bo Chen, Xiangjun Du, Stephen S. Francis, Yuelong Shu, Siyang Liu Tags: Article Source Type: research

A Bayesian approach to Mendelian randomization using summary statistics in the univariable and multivariable settings with correlated pleiotropy
We propose a Bayesian framework for performing Mendelian randomization with potentially pleiotropic genetic instruments. Our proposed method, MR-Horse, is shown to produce unbiased causal effect estimates while avoiding inflated false positive rates, even with high levels of pleiotropy and weak instruments. We further extend the approach to the multivariable setting. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Andrew J. Grant, Stephen Burgess Tags: Article Source Type: research

omicSynth: An open multi-omic community resource for identifying druggable targets across neurodegenerative diseases
Neurodegenerative diseases (NDDs) affect millions of people, and finding genetically supported and effective drug targets has been difficult. Omic data availability and statistical methods can help nominate potential drug targets. We identified 54 NDD-related genes for further functional follow up and drug repurposing. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Chelsea X. Alvarado, Mary B. Makarious, Cory A. Weller, Dan Vitale, Mathew J. Koretsky, Sara Bandres-Ciga, Hirotaka Iwaki, Kristin Levine, Andrew Singleton, Faraz Faghri, Mike A. Nalls, Hampton L. Leonard Tags: Article Source Type: research

Interaction molecular QTL mapping discovers cellular and environmental modifiers of genetic regulatory effects
To identify regulatory variants with plasticity in effect size, we performed interaction molecular quantitative trait loci (iQTL) mapping with cell-type abundance, age, sex, and smoking as the environmental factors. Our results highlight the usefulness of iQTLs for gaining insights into the context specificity of regulatory effects. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Silva Kasela, Fran çois Aguet, Sarah Kim-Hellmuth, Brielin C. Brown, Daniel C. Nachun, Russell P. Tracy, Peter Durda, Yongmei Liu, Kent D. Taylor, W. Craig Johnson, David Van Den Berg, Stacey Gabriel, Namrata Gupta, Joshua D. Smith, Thomas W. Blackwell, Tags: Article Source Type: research

A syndromic neurodevelopmental disorder caused by rare variants in PPFIA3
This study identified 20 individuals with PPFIA3 variants associated with developmental delay, intellectual disability, hypotonia, dysmorphisms, micro/macrocephaly, autistic features, and epilepsy. Functional analysis shows that PPFIA3 variants cause a syndromic neurodevelopmental disorder through a potential loss-of-function mechanism. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Maimuna S. Paul, Sydney L. Michener, Hongling Pan, Hiuling Chan, Jessica M. Pfliger, Jill A. Rosenfeld, Vanesa C. Lerma, Alyssa Tran, Megan A. Longley, Richard A. Lewis, Monika Weisz-Hubshman, Mir Reza Bekheirnia, Nasim Bekheirnia, Lauren Massingham, Mich Tags: Article Source Type: research

An interactive atlas of three-dimensional syndromic facial morphology
We present an online tool for visualizing 3D facial shape variation associated with 95 different genetic syndromes. Our tool allows visualization of variation in severity as well as modulation of facial shape effects with age and by sex. This tool can serve as a diagnostic reference and for training. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: J. David Aponte, Jordan J. Bannister, Hanne Hoskens, Harold Matthews, Kaitlin Katsura, Cassidy Da Silva, Tim Cruz, Julie H.M. Pilz, Richard A. Spritz, Nils D. Forkert, Peter Claes, Francois P. Bernier, Ophir D. Klein, David C. Katz, Benedikt Hallgr ímsso Tags: Article Source Type: research

Building a vertically integrated genomic learning health system: The biobank at the Colorado Center for Personalized Medicine
The CCPM Biobank is a dual-purpose research and clinical resource to accelerate genetic discovery and translation into clinical practice. We have enrolled>200,000 participants and returned genetic findings to thousands. We are uniquely positioned among EHR-linked biobanks, due to our size, integrated learning health system design, and unique catchment area. (Source: The American Journal of Human Genetics)
Source: The American Journal of Human Genetics - January 4, 2024 Category: Genetics & Stem Cells Authors: Laura K. Wiley, Jonathan A. Shortt, Emily R. Roberts, Jan Lowery, Elizabeth Kudron, Meng Lin, David Mayer, Melissa Wilson, Tonya M. Brunetti, Sameer Chavan, Tzu L. Phang, Nikita Pozdeyev, Joseph Lesny, Stephen J. Wicks, Ethan T. Moore, Joshua L. Morgenste Tags: Article Source Type: research