Genetic and Genomic Medicine

Mapping renal impairment and cardiac structure and function: a comprehensive analysis of prospective cohort study, Mendelian randomization and shared genetic etiology

1. Haozhang Huang
2. Jin Liu
3. Xiaozhao Lu
4. Shiqun Chen
5. Yang Zhou
6. Jiyan Chen
7. Ning Tan
8. Wei Jiang
9. Yong Liu

Reviewed by PREreview

Using Networks and Prior Knowledge to Uncover novel Rare Disease Phenotypes

1. Galadriel Brière
2. Cécile Beust
3. Morgane Térézol
4. Anaïs Baudot

Reviewed by PREreview

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. Ian A Glass
23. Jingheng Chen
24. Elizabeth Blue
25. Paolo Prontera
26. Jeremie Rosain
27. Sandrine Marlin
28. Seema R Lalani
29. Hugo J Bellen
30. Undiagnosed Diseases Network

• Curated by eLife

  eLife Assessment

  This important study reveals how Drosophila may be used to investigate the role of missense variants in the PLCG1 phospholipase gene in human diseases. The experimental evidence is compelling and brings together rigorous analysis of clinical and model organism phenotypes with a structural analysis of the PLCG1 protein.

Reviewed by eLife

Functional analysis across model systems implicates ribosomal proteins in growth and proliferation defects associated with hypoplastic left heart syndrome

1. Tanja Nielsen
2. Anaïs Kervadec
3. Jeanne L Theis
4. Maria A Missinato
5. James Marchant
6. Michaela Lynott
7. Aashna Lamba
8. Xin-Xin I Zeng
9. Marie Berenguer
10. Stanley M Walls
11. Analyne Schroeder
12. Katja Birker
13. Greg Duester
14. Paul Grossfeld
15. Timothy J Nelson
16. Timothy M Olson
17. Karen Ocorr
18. Rolf Bodmer
19. Georg Vogler
20. Alexandre R Colas

• Curated by eLife

  eLife Assessment

  This important study applies an innovative multi-model strategy to implicate the ribosomal protein (RP) encoding genes as candidates causing Hypoplastic Left Heart Syndrome. The evidence from the screen in stem cell-derived cardiomyocytes and whole genome sequencing of human patients, followed by functional analyses of RP genes in fly and fish models, is convincing and supports the authors' claims. This work and methodology applied would be of broad interest to medical biologists working on congenital heart diseases.

Reviewed by eLife

Causal associations between plasma proteins and prostate cancer: a Proteome-Wide Mendelian Randomization

1. Chen Lin
2. Rong Zhuona
3. Gu Yanlun
4. Chen Yuke
5. Yu Wei
6. Zhou Ying
7. Pang Xiaocong

• Curated by eLife

  eLife Assessment

  This study presents a valuable meta-analysis of two independent genome-wide association studies (GWASs) elucidating the role of plasma proteins as biomarkers for improving early detection of prostate cancer (PCa). The evidence supporting novel protein biomarkers of PCa risk is solid, although exploration of how these markers may also be shared with other prostate diseases would have strengthened the study. The work will be of interest to the field for elucidating novel variants of prostate cancer risk.

Reviewed by eLife

Confirmation of HLA-II associations with TB susceptibility in admixed African samples

1. Dayna Adrienne Croock
2. Yolandi Swart
3. Haiko Schurz
4. Desiree C Petersen
5. Marlo Möller
6. Caitlin Uren

• Curated by eLife

  eLife Assessment

  This valuable study confirms the association between the human leukocyte antigen (HLA)-II region and tuberculosis (TB) susceptibility in genetically admixed South African populations, specifically identifying a near-genome-wide significant association in the HLA-DPB1 gene, which originates from KhoeSan ancestry. The evidence supporting the association between the HLA-II region and TB susceptibility is solid, and the work will be of interest to those studying the genetic basis of tuberculosis susceptibility/infection resistance.

Reviewed by eLife

Molecular feature-based classification of retroperitoneal liposarcoma: a prospective cohort study

1. Mengmeng Xiao
2. Xiangji Li
3. Fanqin Bu
4. Shixiang Ma
5. Xiaohan Yang
6. Jun Chen
7. Yu Zhao
8. Ferdinando Cananzi
9. Chenghua Luo
10. Li Min

• Curated by eLife

  eLife Assessment

  This study presents a valuable and simplified classification system for predicting clinical outcomes of RPLS patients. The data were collected and analyzed using solid and validated methodology and can be used as a starting point for personalized treatment of RPLS. The work will be of interest to scientists working in the field of RPLS.

Reviewed by eLife

Imputation of structural variants using a multi-ancestry long-read sequencing panel enables identification of disease associations

1. Boris Noyvert
2. A Mesut Erzurumluoglu
3. Dmitriy Drichel
4. Steffen Omland
5. Till FM Andlauer
6. Stefanie Mueller
7. Lau Sennels
8. Christian Becker
9. Aleksandr Kantorovich
10. Boris A Bartholdy
11. Ingrid Brænne
12. Julio Cesar Bolivar-Lopez
13. Costas Mistrellides
14. Gillian M Belbin
15. Jeremiah H Li
16. Joseph K Pickrell
17. Jatin Arora
18. Yao Hu
19. Boehringer Ingelheim – Global Computational Biology and Digital Sciences
20. Clive R Wood
21. Jan M Kriegl
22. Nikhil Podduturi
23. Jan N Jensen
24. Jan Stutzki
25. Zhihao Ding

• Curated by eLife

  eLife Assessment

  This fundamental work significantly enhances our understanding of how structural variants influence human phenotypes. The conclusion is convincingly supported by rigorous analyses of long-read sequencing data. If the raw data are made publicly available, these high-quality datasets and findings will further advance our knowledge of genetic variation in the human population.

Reviewed by eLife

A Titin Missense Variant Causes Atrial Fibrillation

1. Mahmud Arif Pavel
2. Hanna Chen
3. Michael Hill
4. Arvind Sridhar
5. Miles Barney
6. Jaime DeSantiago
7. Asia Owais
8. Shashank Sandu
9. Faisal A Darbar
10. Aylin Ornelas-Loredo
11. Bahaa Al-Azzam
12. Brandon Chalazan
13. Jalees Rehman
14. Dawood Darbar

• Curated by eLife

  eLife Assessment

  The study presents valuable findings regarding the incidence and clinical impact of a mutation in a cardiac muscle protein and its association with the development of atrial fibrillation. The authors provide some convincing evidence of electrophysiological disturbances in cells with this mutation which would be of interest to cellular electrophysiologists. However, evidence supporting the conclusion that this mutation causes atrial fibrillation would benefit from more rigorous electrophysiologic approaches.

Reviewed by eLife

JAK inhibition decreases the autoimmune burden in Down syndrome

1. Angela L Rachubinski
2. Elizabeth Wallace
3. Emily Gurnee
4. Belinda A Enriquez-Estrada
5. Kayleigh R Worek
6. Keith P Smith
7. Paula Araya
8. Katherine A Waugh
9. Ross E Granrath
10. Eleanor Britton
11. Hannah R Lyford
12. Micah G Donovan
13. Neetha Paul Eduthan
14. Amanda A Hill
15. Barry Martin
16. Kelly D Sullivan
17. Lina Patel
18. Deborah J Fidler
19. Matthew D Galbraith
20. Cory A Dunnick
21. David A Norris
22. Joaquín M Espinosa

• Curated by eLife

  eLife Assessment

  Rachubinski and colleagues provide an important manuscript that includes two major advances in understanding immune dysregulation in a large cohort of individuals with Down syndrome. The work comprises compelling, comprehensive, and state-of-the-art clinical, immunological, and autoantibody assessment of autoimmune/inflammatory manifestations. Additionally, the authors report promising results from a clinical trial with the JAK inhibitor tofacitinib for individuals with dermatological autoimmune disease.

Reviewed by eLife