Genetic and Genomic Medicine

A meta-analysis of genome-wide association studies of childhood wheezing phenotypes identifies ANXA1 as a susceptibility locus for persistent wheezing

1. Raquel Granell
2. John A Curtin
3. Sadia Haider
4. Negusse Tadesse Kitaba
5. Sara A Mathie
6. Lisa G Gregory
7. Laura L Yates
8. Mauro Tutino
9. Jenny Hankinson
10. Mauro Perretti
11. Judith M Vonk
12. Hasan S Arshad
13. Paul Cullinan
14. Sara Fontanella
15. Graham C Roberts
16. Gerard H Koppelman
17. Angela Simpson
18. Steve W Turner
19. Clare S Murray
20. Clare M Lloyd
21. John W Holloway
22. Adnan Custovic
23. on behalf of UNICORN and Breathing Together investigators

• Curated by eLife

  eLife assessment

  Genome-wide association studies on asthma have been challenging due to innate heterogeneity and the syndromic nature of asthma, variable accuracy in phenotyping, and potential gene-environment interactions. Here, the authors identified genetic loci associated with subtypes of childhood wheezing in combined data of multiple birth cohorts, by coupling latent class analysis of clinical phenotypic data with GWAS discovery. A mechanistically plausible genetic locus close to annexin 1 (ANXA1) was associated exclusively with early-onset persistent wheeze and provides new translatable molecular insight into asthma pathogenesis.

Reviewed by eLife

Common genetic variations in telomere length genes and lung cancer

1. Ricardo Cortez Cardoso Penha
2. Karl Smith-Byrne
3. Joshua R Atkins
4. Philip Haycock
5. Siddhartha Kar
6. Veryan Codd
7. Nilesh J Samani
8. Christopher P Nelson
9. Maja Milojevic
10. Aurélie AG Gabriel
11. Christopher Amos
12. Paul Brennan
13. Rayjean J Hung
14. Linda Kachuri
15. James D McKay

• Curated by eLife

  eLife assessment

  This study is of interest to epidemiologists and geneticists studying the association between telomere length and lung cancer risk. This work provides useful insight into risk factors for lung cancer. Overall, the results of this study are solid, as the genetic instrument used here is better powered and the battery of MR analysis makes this broad set of results convincing compared to previous work.

Reviewed by eLife

Reserpine maintains photoreceptor survival in retinal ciliopathy by resolving proteostasis imbalance and ciliogenesis defects

1. Holly Y Chen
2. Manju Swaroop
3. Samantha Papal
4. Anupam K Mondal
5. Hyun Beom Song
6. Laura Campello
7. Gregory J Tawa
8. Florian Regent
9. Hiroko Shimada
10. Kunio Nagashima
11. Natalia de Val
12. Samuel G Jacobson
13. Wei Zheng
14. Anand Swaroop

• Curated by eLife

  eLife assessment

  This work provides an important pipeline for high-throughput screening platform to be used for drug discovery. The current data are incomplete. Further validation of human patients-derived iPSC clones and functional assays in mice will strengthen the conclusion.

Reviewed by eLife

Recessive pathogenic variants in MCAT cause combined oxidative phosphorylation deficiency

1. Bryn D Webb
2. Sara M Nowinski
3. Ashley Solmonson
4. Jaya Ganesh
5. Richard J Rodenburg
6. Joao Leandro
7. Anthony Evans
8. Hieu S Vu
9. Thomas P Naidich
10. Bruce D Gelb
11. Ralph J DeBerardinis
12. Jared Rutter
13. Sander M Houten

• Curated by eLife

  eLife assessment

  This paper is a first report of a human subject with an MCAT mutation showing reduced mitochondrial activity, but without defining the molecular mechanism connecting the loss of MCAT activity to mitochondrial dysfunction. It adds to the important field of mitochondrial disease genes and how they impact human physiology.

Reviewed by eLife

Associations of genetic and infectious risk factors with coronary heart disease

1. Flavia Hodel
2. Zhi Ming Xu
3. Christian Wandall Thorball
4. Roxane de La Harpe
5. Prunelle Letang-Mathieu
6. Nicole Brenner
7. Julia Butt
8. Noemi Bender
9. Tim Waterboer
10. Pedro Manuel Marques-Vidal
11. Peter Vollenweider
12. Julien Vaucher
13. Jacques Fellay

• Curated by eLife

  eLife assessment

  This study confirms a role of traditional cardiovascular risk factors (age, sex, cholesterol levels, weight) and polygenetic risk scores when predicting coronary heart disease in a large prospective cohort. It further reports an independent effect of seropositivity from past infection with a commensal bacterium F. nucleatum as a risk factor. The work is based on solid data and methodology and constitutes an important contribution to the understanding of disease risk, but the role of infection needs independent replication.

Reviewed by eLife

Evaluating the effect of metabolic traits on oral and oropharyngeal cancer risk using Mendelian randomization

1. Mark Gormley
2. Tom Dudding
3. Steven J Thomas
4. Jessica Tyrrell
5. Andrew R Ness
6. Miranda Pring
7. Danny Legge
8. George Davey Smith
9. Rebecca C Richmond
10. Emma E Vincent
11. Caroline Bull

• Curated by eLife

  eLife assessment

  This is an important study linking metabolic traits and head and neck cancer risk using Mendelian randomisation. The findings, well supported by the data, were inconclusive. This work will be of interest to researchers working in head and neck cancer.

Reviewed by eLife

Regulatory de novo mutations underlying intellectual disability

1. Matias G De Vas
2. Fanny Boulet
3. Shweta S Joshi
4. Myles G Garstang
5. Tahir N. Khan
6. Goutham Atla
7. David Parry
8. David Moore
9. Inês Cebola
10. Shuchen Zhang
11. Wei Cui
12. Anne K Lampe
13. Wayne W Lam
14. Genomics England Research Consortium
15. Jorge Ferrer
16. Madapura M Pradeepa
17. Santosh S Atanur

Reviewed by Review Commons

Polygenic risk scores for the prediction of common cancers in East Asians: A population-based prospective cohort study

1. Peh Joo Ho
2. Iain BeeHuat Tan
3. Dawn Qingqing Chong
4. Chiea Chuen Khor
5. Jian-Min Yuan
6. Woon-Puay Koh
7. Rajkumar Dorajoo
8. Jingmei Li

• Curated by eLife

  eLife assessment

  This important study reveals the role of polygenic scores for four commonly diagnosed cancers with high genetic predisposition (breast, prostate, colorectal, and lung) in East Asian populations, which is developed in participants of European descent. The data is convincing that is derived from a prospective cohort including 21,694 Singaporean participants of East Asian descent. The work will be of interest and provide great help to disease specialists in the field.

Reviewed by eLife

A Progeroid Syndrome Caused by RAF1 deficiency Underscores the importance of RTK signaling for Human Development

1. Samantha Wong
2. Yu Xuan Tan
3. Kiat Yi Tan
4. Abigail Loh
5. Zainab Aziz
6. Engin Özkan
7. Hülya Kayserili
8. Nathalie Escande-Beillard
9. Bruno Reversade

Reviewed by Review Commons

The missing link between genetic association and regulatory function

1. Noah J Connally
2. Sumaiya Nazeen
3. Daniel Lee
4. Huwenbo Shi
5. John Stamatoyannopoulos
6. Sung Chun
7. Chris Cotsapas
8. Christopher A Cassa
9. Shamil R Sunyaev

• Curated by eLife

  eLife assessment

  A commonly held hypothesis about how genetic variants predispose to common diseases and other human traits is that variants have phenotypic effects by altering transcript accumulation. The authors question this view by showing some evidence for shared genetic control of transcript abundance for genes believed to be involved in the traits, and for the traits themselves.

Reviewed by eLife