Genetic and Genomic Medicine

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

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

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

Estimating bone marrow adiposity from head MRI and identifying its genetic architecture

1. Tobias Kaufmann
2. Pål Marius Bjørnstad
3. Martin Falck
4. Stener Nerland
5. Kevin O’Connell
6. Oleksandr Frei
7. Ole A Andreassen
8. Lars T Westlye
9. Srdjan Djurovic
10. Timothy Hughes

• Curated by eLife

  eLife Assessment

  This solid paper reports on the use of artificial intelligence to assess bone marrow adipose tissue in the skull. The method employing MRI is novel and that approach allows for the identification of genetic loci that regulate this trait as well as others using data from the UK biobank. Overall this is an important contribution although the authors should consider several points: 1-validation of the T1-weighted MRI signal intensity; 2-further discussion of the sex differences; and 3-cross-trait linkage disequilibrium score regression (LDSC) for osteoporosis, Parkinson's disease, and cognitive function.

Reviewed by eLife

Novel risk loci for COVID-19 hospitalization among admixed American populations

1. Silvia Diz-de Almeida
2. Raquel Cruz
3. Andre D Luchessi
4. José M Lorenzo-Salazar
5. Miguel López de Heredia
6. Inés Quintela
7. Rafaela González-Montelongo
8. Vivian Nogueira Silbiger
9. Marta Sevilla Porras
10. Jair Antonio Tenorio Castaño
11. Julian Nevado
12. Jose María Aguado
13. Carlos Aguilar
14. Sergio Aguilera-Albesa
15. Virginia Almadana
16. Berta Almoguera
17. Nuria Alvarez
18. Álvaro Andreu-Bernabeu
19. Eunate Arana-Arri
20. Celso Arango
21. María J Arranz
22. Maria-Jesus Artiga
23. Raúl C Baptista-Rosas
24. María Barreda- Sánchez
25. Moncef Belhassen-Garcia
26. Joao F Bezerra
27. Marcos AC Bezerra
28. Lucía Boix-Palop
29. María Brion
30. Ramón Brugada
31. Matilde Bustos
32. Enrique J Calderón
33. Cristina Carbonell
34. Luis Castano
35. Jose E Castelao
36. Rosa Conde-Vicente
37. M Lourdes Cordero-Lorenzana
38. Jose L Cortes-Sanchez
39. Marta Corton
40. M Teresa Darnaude
41. Alba De Martino-Rodríguez
42. Victor del Campo-Pérez
43. Aranzazu Diaz de Bustamante
44. Elena Domínguez-Garrido
45. Rocío Eirós
46. María Carmen Fariñas
47. María J Fernandez-Nestosa
48. Uxía Fernández-Robelo
49. Amanda Fernández-Rodríguez
50. Tania Fernández-Villa
51. Manuela Gago-Dominguez
52. Belén Gil-Fournier
53. Javier Gómez-Arrue
54. Beatriz González Álvarez
55. Fernan Gonzalez Bernaldo de Quirós
56. Anna González-Neira
57. Javier González-Peñas
58. Juan F Gutiérrez-Bautista
59. María José Herrero
60. Antonio Herrero-Gonzalez
61. María A Jimenez-Sousa
62. María Claudia Lattig
63. Anabel Liger Borja
64. Rosario Lopez-Rodriguez
65. Esther Mancebo
66. Caridad Martín-López
67. Vicente Martín
68. Oscar Martinez-Nieto
69. Iciar Martinez-Lopez
70. Michel F Martinez-Resendez
71. Angel Martinez-Perez
72. Juliana F Mazzeu
73. Eleuterio Merayo Macías
74. Pablo Minguez
75. Victor Moreno Cuerda
76. Silviene F Oliveira
77. Eva Ortega-Paino
78. Mara Parellada
79. Estela Paz-Artal
80. Ney PC Santos
81. Patricia Pérez-Matute
82. Patricia Perez
83. M Elena Pérez-Tomás
84. Teresa Perucho
85. Mellina Pinsach-Abuin
86. Guillermo Pita
87. Ericka N Pompa-Mera
88. Gloria L Porras-Hurtado
89. Aurora Pujol
90. Soraya Ramiro León
91. Salvador Resino
92. Marianne R Fernandes
93. Emilio Rodríguez-Ruiz
94. Fernando Rodriguez-Artalejo
95. José A Rodriguez-Garcia
96. Francisco Ruiz-Cabello
97. Javier Ruiz-Hornillos
98. Pablo Ryan
99. José Manuel Soria
100. Juan Carlos Souto
101. Eduardo Tamayo
102. Alvaro Tamayo-Velasco
103. Juan Carlos Taracido-Fernandez
104. Alejandro Teper
105. Lilian Torres-Tobar
106. Miguel Urioste
107. Juan Valencia-Ramos
108. Zuleima Yáñez
109. Ruth Zarate
110. Itziar de Rojas
111. Agustín Ruiz
112. Pascual Sánchez
113. Luis Miguel Real
114. SCOURGE Cohort Group
115. Encarna Guillen-Navarro
116. Carmen Ayuso
117. Esteban Parra
118. José A Riancho
119. Augusto Rojas-Martinez
120. Carlos Flores
121. Pablo Lapunzina
122. Ángel Carracedo

• Curated by eLife

  eLife assessment

  The authors conduct a valuable GWAS meta-analysis for COVID-19 hospitalization in admixed American populations and prioritized risk variants and genes. The evidence supporting the claims of the authors is solid. The work will be of interest to scientists studying the genetic basis of COVID pathogenesis.

Reviewed by eLife

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