Genetic and Genomic Medicine

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. Joaquin 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

Low-dose chemotherapy combined with delayed immunotherapy in the neoadjuvant treatment of non-small cell lung cancer and dynamic monitoring of the drug response in peripheral blood

1. Chaoyang Liang
2. Qi Song
3. Wenhao Zhou
4. Na Li
5. Qi Xiong
6. Chaohu Pan
7. Shaohong Zhao
8. Xiang Yan
9. Xiaoling Zhang
10. Yaping Long
11. Juntang Guo
12. Tao Wang
13. Weiwei Shi
14. Shengjie Sun
15. Bo Yang
16. Zhouhuan Dong
17. Haitao Luo
18. Jie Li
19. Yi Hu
20. Bo Yang

• Curated by eLife

  eLife Assessment

  Liang et al. have conducted a small pilot study investigating the feasibility and tolerability of a regimen of neoadjuvant chemo-immunotherapy for non-small cell lung cancer; with lower cumulative dose of chemotherapy and with the immunotherapy delivered on D8 of each cycle. The clinical data are interesting and novel, and overall the findings of the study are valuable. However, the translational data and analyses are incomplete and do not support key claims in the title.

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

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

1. Dayna 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. Whilst some of the evidence supporting the association between the HLA-II region and TB susceptibility is solid, the analysis is incomplete and requires further work for the study to achieve its full value. The work will be of interest to those studying the genetic basis of tuberculosis susceptibility/infection resistance.

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

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