Genetic and Genomic Medicine

The genetic risk of gestational diabetes in South Asian women

1. Amel Lamri
2. Jayneel Limbachia
3. Karleen M Schulze
4. Dipika Desai
5. Brian Kelly
6. Russell J de Souza
7. Guillaume Paré
8. Deborah A Lawlor
9. John Wright
10. Sonia S Anand
11. On behalf of for the Born in Bradford and START investigators

• Curated by eLife

  eLife assessment

  This paper asks whether a risk score integrating the impact of common genetic variants across the genome (polygenic risk score) on Type II Diabetes is also to any degree predictive of diabetes in pregnancy (Gestational diabetes or GDM).The study population comprises women of South Asian ancestry, who are particularly susceptible to GDM. Strong evidence is presented in favour of the hypothesis of the hypothesis in two sizeable cohorts, one from Canada and the other from the UK. The paper will be useful to those studying women's health in pregnancy, and in particular GDM, which is associated with a number of adverse pregnancy outcomes.

Reviewed by eLife

Phenome-wide Mendelian randomization study of plasma triglyceride levels and 2600 disease traits

1. Joshua K Park
2. Shantanu Bafna
3. Iain S Forrest
4. Áine Duffy
5. Carla Marquez-Luna
6. Ben O Petrazzini
7. Ha My Vy
8. Daniel M Jordan
9. Marie Verbanck
10. Jagat Narula
11. Robert S Rosenson
12. Ghislain Rocheleau
13. Ron Do

• Curated by eLife

  eLife assessment

  This manuscript will be of interest to cardiovascular clinicians, medical geneticists, pharmaceutical companies, and the general cardiovascular disease research community. The study adds evidence for the causal role of triglyceride to several atherosclerotic cardiovascular diseases. Their use of Mendelian Randomization method is appropriate and provides convincing support to their findings, which may provide insights on the mechanism of TG biology and drug repurposing of TG-lowering agents.

Reviewed by eLife

Personality traits are consistently associated with blood mitochondrial DNA copy number estimated from genome sequences in two genetic cohort studies

1. Richard F Oppong
2. Antonio Terracciano
3. Martin Picard
4. Yong Qian
5. Thomas J Butler
6. Toshiko Tanaka
7. Ann Zenobia Moore
8. Eleanor M Simonsick
9. Krista Opsahl-Ong
10. Christopher Coletta
11. Angelina R Sutin
12. Myriam Gorospe
13. Susan M Resnick
14. Francesco Cucca
15. Sonja W Scholz
16. Bryan J Traynor
17. David Schlessinger
18. Luigi Ferrucci
19. Jun Ding

• Curated by eLife

  Evaluation Summary:

  This paper makes a comprehensive survey of the relationship between mtDNAcn and the personality dimensions, as well as how and whether they mediate the relationships between personality dimensions and mortability as well as other behavioural measures that may lead to mortality. More work needs to be performed to truly understand the relationship between personality dimensions and mortality, as well as the physiological traits (like mtDNAcn) that may be mediating it.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 agreed to share their name with the authors.)

Reviewed by eLife

Mitochondrial MICOS complex genes, implicated in hypoplastic left heart syndrome, maintain cardiac contractility and actomyosin integrity

1. Katja Birker
2. Shuchao Ge
3. Natalie J Kirkland
4. Jeanne L Theis
5. James Marchant
6. Zachary C Fogarty
7. Maria A Missinato
8. Sreehari Kalvakuri
9. Paul Grossfeld
10. Adam J Engler
11. Karen Ocorr
12. Timothy J Nelson
13. Alexandre R Colas
14. Timothy M Olson
15. Georg Vogler
16. Rolf Bodmer

Reviewed by Review Commons

Constructing an atlas of associations between polygenic scores from across the human phenome and circulating metabolic biomarkers

1. Si Fang
2. Michael V Holmes
3. Tom R Gaunt
4. George Davey Smith
5. Tom G Richardson

• Curated by eLife

  Evaluation Summary:

  The authors describe their work on an atlas of associations between polygenic scores for 129 different traits representing a variety of quantitative phenotypes and diseases, and a large set of metabolites measured in up to 83,000 participants in the UK Biobank. These associations are all available via a public browser, and may be used to identify candidate intermediate phenotypes, as well as potential biomarkers of disease.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #2 and Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Diverse ancestry whole-genome sequencing association study identifies TBX5 and PTK7 as susceptibility genes for posterior urethral valves

1. Melanie MY Chan
2. Omid Sadeghi-Alavijeh
3. Filipa M Lopes
4. Alina C Hilger
5. Horia C Stanescu
6. Catalin D Voinescu
7. Glenda M Beaman
8. William G Newman
9. Marcin Zaniew
10. Stefanie Weber
11. Yee Mang Ho
12. John O Connolly
13. Dan Wood
14. Carlo Maj
15. Alexander Stuckey
16. Athanasios Kousathanas
17. Genomics England Research Consortium
18. Robert Kleta
19. Adrian S Woolf
20. Detlef Bockenhauer
21. Adam P Levine
22. Daniel P Gale

• Curated by eLife

  Evaluation Summary:

  Prior work has linked posterior urethral valves (PUV), a common cause of end stage renal disease in children, with chromosomal abnormalities and rare copy number variants, but the genetic causes of PUV remain incompletely defined. In this study, the authors have used diverse ancestry whole-genome sequencing association studies to identify two novel genes and an enrichment of rare duplications and inversions affecting candidate cis-regulatory elements as possible causes of this rare condition, illustrating the potential for this approach to other rare conditions.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #3 agreed to share their name with the authors.)

Reviewed by eLife

Age acquired skewed X chromosome inactivation is associated with adverse health outcomes in humans

1. Amy L Roberts
2. Alessandro Morea
3. Ariella Amar
4. Antonino Zito
5. Julia S El-Sayed Moustafa
6. Max Tomlinson
7. Ruth CE Bowyer
8. Xinyuan Zhang
9. Colette Christiansen
10. Ricardo Costeira
11. Claire J Steves
12. Massimo Mangino
13. Jordana T Bell
14. Chloe CY Wong
15. Timothy J Vyse
16. Kerrin S Small

• Curated by eLife

  Evaluation Summary:

  Women are a mosaic of two population of cells, one with the paternal X-chromosome and the other with the maternal one in the active state due to random X-chromosome inactivation (XCI) that occurs during embryogenesis. During aging, one of the two populations dominates the other in a significant proportion of women. This skewing of XCI is of unknown etiology and its impact on health remains enigmatic. In this study, Amy L. Robert et al, demonstrate that skewing may not be benign and it is associated with a modest but significant increased risk of cardiovascular disease and cancer.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

Trio-based whole exome sequencing in patients with suspected sporadic inborn errors of immunity: A retrospective cohort study

1. Anne Hebert
2. Annet Simons
3. Janneke HM Schuurs-Hoeijmakers
4. Hans JPM Koenen
5. Evelien Zonneveld-Huijssoon
6. Stefanie SV Henriet
7. Ellen JH Schatorjé
8. Esther PAH Hoppenreijs
9. Erika KSM Leenders
10. Etienne JM Janssen
11. Gijs WE Santen
12. Sonja A de Munnik
13. Simon V van Reijmersdal
14. Esther van Rijssen
15. Simone Kersten
16. Mihai G Netea
17. Ruben L Smeets
18. Frank L van de Veerdonk
19. Alexander Hoischen
20. Caspar I van der Made

• Curated by eLife

  Evaluation Summary:

  This study reports on the diagnostic utility of TRIO-based whole-exome sequencing (WES) in a cohort of 123 unrelated patients with suspected monogenic inborn errors of immunity. The authors further explored the diagnostic rate in this cohort by focusing their analyses on the identification of de novo variants (DNVs). This manuscript will be of interest to medical geneticists, immunologists, and physicians working with patients with primary immunodeficiencies.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)

Reviewed by eLife

Genomic landscape of lymphatic malformations: a case series and response to the PI3Kα inhibitor alpelisib in an N-of-1 clinical trial

1. Montaser F Shaheen
2. Julie Y Tse
3. Ethan S Sokol
4. Margaret Masterson
5. Pranshu Bansal
6. Ian Rabinowitz
7. Christy A Tarleton
8. Andrey S Dobroff
9. Tracey L Smith
10. Thèrése J Bocklage
11. Brian K Mannakee
12. Ryan N Gutenkunst
13. Joyce Bischoff
14. Scott A Ness
15. Gregory M Riedlinger
16. Roman Groisberg
17. Renata Pasqualini
18. Shridar Ganesan
19. Wadih Arap

• Curated by eLife

  Evaluation Summary:

  This manuscript could be of interest to physicians and researchers in the field of vascular anomalies. The cohort of patients with lymphatic malformations is reasonably sized (n=30) and the claims made by the authors are supported by the data as well as by current knowledge in the field.

  (This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. Reviewer #1 agreed to share their name with the authors.)

Reviewed by eLife

SARS-CoV-2 genomic surveillance in Rwanda: Introductions and local transmission of the B.1.617.2 (Delta) variant of concern

1. Yvan Butera
2. Samuel L. Hong
3. Muhammed Semakula
4. Nena Bollen
5. Verity Hill
6. Áine Niamh O’Toole
7. Barney I. Potter
8. Dieudonné Mutangana
9. Reuben Sindayiheba
10. Robert Rutayisire
11. Maria Artesi
12. Vincent Bours
13. Nadine Rujeni
14. Simon Dellicour
15. Keith Durkin
16. Leon Mutesa
17. Guy Baele

Reviewed by ScreenIT