Genetic and Genomic Medicine

Novel discoveries and enhanced genomic prediction from modelling genetic risk of cancer age-at-onset

1. Ekaterina S. Maksimova
2. Sven E. Ojavee
3. Kristi Läll
4. Marie C. Sadler
5. Reedik Mägi
6. Zoltan Kutalik
7. Matthew R. Robinson

• Curated by eLife

  eLife assessment

  This manuscript is a useful contribution to the field of complex trait genomics. The study does have some real strengths, such as focusing on cancer age-of-onset, developing methods for this unusual trait and using two cohorts. However, the significance of findings is difficult to evaluate without further comparisons and validations, leaving the work in its current form incomplete.

Reviewed by eLife

Multi-omics analysis in human retina uncovers ultraconserved cis -regulatory elements at rare eye disease loci

1. Victor Lopez Soriano
2. Alfredo Dueñas Rey
3. Rajarshi Mukherjee
4. Genomics England Research Consortium
5. Frauke Coppieters
6. Miriam Bauwens
7. Andy Willaert
8. Elfride De Baere

Reviewed by Review Commons

Trumpet plots: Visualizing The Relationship Between Allele Frequency And Effect Size In Genetic Association Studies

1. Lucia Corte
2. Lathan Liou
3. Paul F. O’Reilly
4. Judit García-González

• Curated by GigaByte

  **Editors Assessment: **

  This work presents a new standardized graphical approach for visualizing genetic associations across a wide range of allele frequencies. These proposed TrumpetPlots have a distinctive trumpet shape, hence the proposed name. With the majority of variants having low frequency and small effects, while a small number of variants have higher frequency and larger effects, this view can help to provide new and valuable insights into the genetic basis of traits and diseases, and also help prioritize efforts to discover new risk variants. The tool is provided as a novel R package and R Shiny application and to demonstrate its use the article illustrates the distribution of variant effect sizes across the allele frequency range for over 100 continuous traits available in the UK Biobank. After some problems in testing the package is now available and easy to deploy via CRAN.

  *This assessment refers to version 1 of this preprint. *

Reviewed by GigaByte

Genetic inactivation of zinc transporter SLC39A5 improves liver function and hyperglycemia in obesogenic settings

1. Shek Man Chim
2. Kristen Howell
3. John Dronzek
4. Weizhen Wu
5. Cristopher Van Hout
6. Manuel AR Ferreira
7. Bin Ye
8. Alexander Li
9. Susannah Brydges
10. Vinayagam Arunachalam
11. Anthony Marcketta
12. Adam E Locke
13. Jonas Bovijn
14. Niek Verweij
15. Tanima De
16. Luca Lotta
17. Lyndon Mitnaul
18. Michelle LeBlanc
19. Regeneron Genetics Center
20. David J Carey
21. Olle Melander
22. Alan Shuldiner
23. Katia Karalis
24. Aris N Economides
25. Harikiran Nistala
26. DiscovEHR collaboration
27. Regeneron Genetics Center

• Curated by eLife

  eLife assessment

  This fundamental study substantially advances our understanding of the role of zinc in metabolism, specifically a newly established clinical link between mutations in the zinc transporter SLC39A5, elevated serum zinc levels, and a reduction in the risk of Type 2 Diabetes. The provided evidence is solid with state-of-the-art genetic analysis of large human cohorts followed by a comprehensive analysis of a mouse SLC39A5 knockout mutant, establishing that SLC39A5 plays a role in hepatic lipid handling through AMPK signaling, although the limited analysis of a pancreatic phenotype that has previously been described constitutes a weakness. This study will be of relevance to researchers interested in metabolism, fatty liver disease, and the biology of trace elements.

Reviewed by eLife

Association between APOL1 risk variants and the occurrence of sepsis in Black patients hospitalized with infections: a retrospective cohort study

1. Lan Jiang
2. Ge Liu
3. Annette Oeser
4. Andrea Ihegword
5. Alyson L Dickson
6. Laura L Daniel
7. Adriana M Hung
8. Nancy J Cox
9. Cecilia P Chung
10. Wei-Qi Wei
11. C Michael Stein
12. Qiping Feng

• Curated by eLife

  eLife assessment

  In this valuable study, patients homozygous for both minor frequency alleles of the APOL1 gene are shown to be at significant risk for progression into sepsis after infection. The study has enrolled a significant number of subjects and provides solid results. The study addresses to infectious diseases and critical care experts and one major weakness is the lack of inclusion of non-Black patients.

Reviewed by eLife

Polymorphisms in Intron 1 of HLA-DRA Differentially Associate with Type 1 Diabetes and Celiac Disease and Implicate Involvement of Complement System Genes C4A and C4B

1. Özkan Aydemir
2. Jeffrey A. Bailey
3. Daniel Agardh
4. Åke Lernmark
5. Janelle A. Noble
6. Agnes Andersson Svärd
7. Elizabeth P. Blankenhorn
8. Hemang Parikh
9. Anette-G. Ziegler
10. Jorma Toppari
11. Beena Akolkar
12. William A. Hagopian
13. Marian J. Rewers
14. John P. Mordes
15. TEDDY Study Group

• Curated by eLife

  eLife assessment

  This study presents valuable findings on genetic risk factors for type 1 diabetes and celiac disease using a large cohort from the Environmental Determinants of Diabetes in the Young (TEDDY) study. The evidence supporting the claims of the authors is solid, although the inclusion of the genetic effect of this locus on individuals with different genetic backgrounds would have strengthened the study. The work will be of interest to population geneticists working on diabetes and celiac disease.

Reviewed by eLife

PYCR1 Levels Track with Premature and Chronological Skin Aging

1. Kortessa Sotiropoulou
2. Saniye Yumlu
3. Tomoko Hirano
4. Michael Maier
5. Abigail Loh
6. Peh Fern Ong
7. Onn Siong Yim
8. Chunping Liu
9. Emmanuel Vial
10. Umut Altunoğlu
11. Sheela Nampoothiri
12. Deepthi de Silva
13. Björn Fischer-Zirnsak
14. Hülya Kayserili
15. Poh San Lai
16. Oliver Dreesen
17. Kenji Kabashima
18. Uwe Kornak
19. Nathalie Escande-Beillard
20. Bruno Reversade

• Curated by eLife

  eLife assessment

  This manuscript uses genetic mouse modeling to delve deeper into a rare human disease of aging. The targeted approaches employed lend greater pathophysiologic insight and makes this paper valuable to the field art large. Additionally, the approaches used are rigorous and solid in supporting their conclusions. Some minor weaknesses were noted along with suggestions to add greater clarity.

Reviewed by eLife, preLights

Genetic associations for two biological age measures point to distinct aging phenotypes

1. Chia‐Ling Kuo
2. Luke C. Pilling
3. Zuyun Liu
4. Janice L. Atkins
5. Morgan E. Levine

Reviewed by ScreenIT

SARS-CoV-2 spread across the Colombian-Venezuelan border

1. Alberto Paniz-Mondolfi
2. Marina Muñoz
3. Carolina Florez
4. Sergio Gomez
5. Angelica Rico
6. Lisseth Pardo
7. Esther C. Barros
8. Carolina Hernández
9. Lourdes Delgado
10. Jesús E. Jaimes
11. Luis Pérez
12. Aníbal A. Teherán
13. Hala Alejel Alshammary
14. Ajay Obla
15. Zenab Khan
16. Jayeeta Dutta
17. Adriana van de Guchte
18. Ana S. Gonzalez-Reiche
19. Matthew M. Hernandez
20. Emilia Mia Sordillo
21. Viviana Simon
22. Harm van Bakel
23. Martin S. Llewellyn
24. Juan David Ramírez

Reviewed by ScreenIT

Polymorphisms in the ACE2 Locus Associate with Severity of COVID-19 Infection

1. Luke Wooster
2. Christopher J. Nicholson
3. Haakon H. Sigurslid
4. Christian L. Lino Cardenas
5. Rajeev Malhotra

Reviewed by ScreenIT