Genetic and Genomic Medicine

Genotype-specific differences in infertile men due to loss-of-function variants in M1AP or ZZS genes

1. Nadja Rotte
2. Jessica E.M. Dunleavy
3. Michelle D. Runkel
4. Daniela Fietz
5. Adrian Pilatz
6. Johanna Kuss
7. Ann-Kristin Dicke
8. Sofia B. Winge
9. Sara Di Persio
10. Christian Ruckert
11. Verena Nordhoff
12. Hans-Christian Schuppe
13. Kristian Almstrup
14. Sabine Kliesch
15. Nina Neuhaus
16. Birgit Stallmeyer
17. Moira K. O’Bryan
18. Frank Tüttelmann
19. Corinna Friedrich

Reviewed by Review Commons

Genomic landscape of endometrial, ovarian and cervical cancers in Japan from database in the Center for Cancer Genomics and Advanced Therapeutics

1. Qian Xi
2. Hidenori Kage
3. Miho Ogawa
4. Asami Matsunaga
5. Akira Nishijima
6. Kenbun Sone
7. Kei Kawana
8. Katsutoshi Oda

Reviewed by PREreview

Ethnic and region-specific genetic risk variants of stroke and its comorbid conditions can define the variations in the burden of stroke and its phenotypic traits

1. Rashmi Sukumaran
2. Achuthsankar S Nair
3. Moinak Banerjee

• Curated by eLife

  eLife assessment

  This paper provides a useful analysis of the variation of the burden of strokes across geographic regions, finding differences in the relationship between strokes and their comorbidities. This dataset and the correlations found within will be a resource for directing the focus of future investigations. The results are technically solid, but there are cases where statistical analyses are yet to be carried out to support statements of statistical significance.

Reviewed by eLife

Risk factors affecting polygenic score performance across diverse cohorts

1. Daniel Hui
2. Scott Dudek
3. Krzysztof Kiryluk
4. Theresa L Walunas
5. Iftikhar J Kullo
6. Wei-Qi Wei
7. Hemant Tiwari
8. Josh F Peterson
9. Wendy K Chung
10. Brittney H Davis
11. Atlas Khan
12. Leah C Kottyan
13. Nita A Limdi
14. Qiping Feng
15. Megan J Puckelwartz
16. Chunhua Weng
17. Johanna L Smith
18. Elizabeth W Karlson
19. Regeneron Genetics Center
20. Penn Medicine BioBank
21. Gail P Jarvik
22. Marylyn D Ritchie

• Curated by eLife

  eLife assessment

  This study presents a convincing analysis of the effects of covariates, such as age, sex, socio-economic status, or biomarker levels, on the predictive accuracy of polygenic scores for body mass index; The work is further supported by important approaches for improving prediction accuracy by accounting for such covariates across a variety of association studies. The authors did a commendable job addressing reviewer suggestions and comments. The work will be of interest to colleagues using and developing methods for phenotypic prediction based on polygenic scores.

Reviewed by eLife

De novo variants in PLCG1 are associated with hearing impairment, ocular pathology, and cardiac defects

1. Mengqi Ma
2. Yiming Zheng
3. Shenzhao Lu
4. Xueyang Pan
5. Kim C. Worley
6. Lindsay C. Burrage
7. Lauren S. Blieden
8. Aimee Allworth
9. Wei-Liang Chen
10. Giuseppe Merla
11. Barbara Mandriani
12. Jill A. Rosenfeld
13. David Li-Kroeger
14. Debdeep Dutta
15. Shinya Yamamoto
16. Michael F. Wangler
17. Undiagnosed Diseases Network
18. Ian A. Glass
19. Sam Strohbehn
20. Elizabeth Blue
21. Paolo Prontera
22. Seema R. Lalani
23. Hugo J. Bellen

• Curated by eLife

  eLife assessment

  This important study reveals how Drosophila may be used to investigate the role of missense variants in the gene PLCG1 related to human disease in case studies. The evidence that most of these variants have a gain-of-function effect in the fly is convincing and supportive of their pathogenic effect. With some additional control experiments to assess overexpression toxicity, this work would be of relevance to human and Drosophila geneticists alike.

Reviewed by eLife

Discovery of runs-of-homozygosity diplotype clusters and their associations with diseases in UK Biobank

1. Ardalan Naseri
2. Degui Zhi
3. Shaojie Zhang

• Curated by eLife

  eLife assessment

  This study is of potential interest to readers in human genetics and quantitative genetics, as it presents a new method for homozygosity mapping in population-scale datasets, based on an innovative computational algorithm that efficiently identifies runs-of-homozygosity (ROH) segments shared by many individuals. Although the method is innovative and has the potential to be broadly useful, its power and limitations have not yet been adequately evaluated. The application of this new method to the UK Biobank dataset identifies several interesting associations, but it remains currently unclear under what conditions the new approach can provide additional power over existing genome-wide association study methods.

Reviewed by eLife

Explaining the counter-intuitive effectiveness of trophectoderm biopsy for PGT-A using computational modelling

1. Benjamin M Skinner
2. Manuel Viotti
3. International Registry of Mosaic Embryo Transfers (IRMET)
4. Darren K Griffin
5. Peter JI Ellis

• Curated by eLife

  eLife assessment

  This study presents a valuable computational model for elaborating on the interpretation of chromosomal mosaicism in preimplantation embryos. The evidence supporting the claims of the authors is incomplete due to the assumption that is possible to quantify the cells in the embryo, oversimplification of mitotic errors, and the inclusion of the self-correction premise. The work will be of interest to embryologists, and geneticists working on reproductive medicine.

Reviewed by eLife

Allelic strengths of encephalopathy-associated UBA5 variants correlate between in vivo and in vitro assays

1. Xueyang Pan
2. Albert N Alvarez
3. Mengqi Ma
4. Shenzhao Lu
5. Michael W Crawford
6. Lauren C Briere
7. Oguz Kanca
8. Shinya Yamamoto
9. David A Sweetser
10. Jenny L Wilson
11. Ruth J Napier
12. Jonathan N Pruneda
13. Hugo J Bellen

• Curated by eLife

  eLife assessment

  The authors establish a Drosophila model to assess the severity of disease-linked alleles of Uba5. Using both in vivo and in vitro experiments, this valuable study demonstrates the alleles fall into mild, intermediate, and severe classes, with convincing evidence to support their conclusion. This well-executed study establishes a model for further characterization of Uba5-related phenotypes in a powerful model system.

Reviewed by eLife

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