Genetic and Genomic Medicine

Statistical examination of shared loci in neuropsychiatric diseases using genome-wide association study summary statistics

1. Thomas P Spargo
2. Lachlan Gilchrist
3. Guy P Hunt
4. Richard JB Dobson
5. Petroula Proitsi
6. Ammar Al-Chalabi
7. Oliver Pain
8. Alfredo Iacoangeli

• Curated by eLife

  eLife assessment

  This paper presents a valuable pipeline based on state-of-the-art analytical software that was used to study genetic pleiotropy between neuropsychiatric disorders. The presented evidence supporting the claims is convincing and now includes an appropriate comparison to previously published methods as well as a detailed exploration of the findings. The created pipeline can thus be used by researchers from diverse fields to study different combinations of diseases and traits.

Reviewed by eLife

Maternal smoking DNA methylation risk score associated with health outcomes in offspring of European and South Asian ancestry

1. Wei Q Deng
2. Nathan Cawte
3. Natalie Campbell
4. Sandi M Azab
5. Russell J de Souza
6. Amel Lamri
7. Katherine M Morrison
8. Stephanie A Atkinson
9. Padmaja Subbarao
10. Stuart E Turvey
11. Theo J Moraes
12. Koon K Teo
13. Piush J Mandhane
14. Meghan B Azad
15. Elinor Simons
16. Guillaume Paré
17. Sonia S Anand

• Curated by eLife

  eLife assessment

  This study offers a useful advance by introducing a cord blood DNA methylation score for maternal smoking effects, with the inclusion of cohorts from diverse backgrounds. However, the overall strength of evidence is deemed incomplete, due to concerns regarding low exposure levels and low statistical power, which hampers the generalisability of their findings. The study provides an interesting basis for future studies, but would benefit from the addition of more cohorts to validate the findings and a focus on more diverse health outcomes.

Reviewed by eLife

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

Heterozygous variants in PLCG1 affect hearing, vision, cardiac, and immune function

1. Mengqi Ma
2. Yiming Zheng
3. Mingxi Deng
4. Shenzhao Lu
5. Xueyang Pan
6. Xi Luo
7. Michelle Etoundi
8. David Li-Kroeger
9. Kim C. Worley
10. Lindsay C. Burrage
11. Lauren S. Blieden
12. Aimee Allworth
13. Wei-Liang Chen
14. Giuseppe Merla
15. Barbara Mandriani
16. Catherine E Otten
17. Pierre Blanc
18. Jill A. Rosenfeld
19. Debdeep Dutta
20. Shinya Yamamoto
21. Michael F. Wangler
22. Undiagnosed Diseases Network
23. Ian A. Glass
24. Jingheng Chen
25. Elizabeth Blue
26. Paolo Prontera
27. Jeremie Rosain
28. Sandrine Marlin
29. Seema R. Lalani
30. 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