Genetic and Genomic Medicine

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 N 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-Domínguez
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. Ángel 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. Mel·lina 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

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

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 K. Tiwari
8. Josh F. Peterson
9. Wendy K. Chung
10. Brittney Davis
11. Atlas Khan
12. Leah 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. Gail P. Jarvik
21. 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

De novo variants in PLCG1 are associated with hearing impairment, ocular pathology, and cardiac defects

1. Mengqi Ma
2. Yiming Zheng
3. Shenzhao Lu
4. Xueyang Pan
5. Kim C. Worley
6. Lindsay C. Burrage
7. Lauren S. Blieden
8. Aimee Allworth
9. Wei-Liang Chen
10. Giuseppe Merla
11. Barbara Mandriani
12. Jill A. Rosenfeld
13. David Li-Kroeger
14. Debdeep Dutta
15. Shinya Yamamoto
16. Michael F. Wangler
17. Undiagnosed Diseases Network
18. Ian A. Glass
19. Sam Strohbehn
20. Elizabeth Blue
21. Paolo Prontera
22. Seema R. Lalani
23. 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