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| Open AccessFormalising recall by genotype as an efficient approach to detailed phenotyping and causal inference
Recall-by-Genotype (RbG) is an approach to recall participants from genetic studies based on their specific genotype for further, more extensive phenotyping. Here, the authors discuss examples of RbG as well as practical and ethical considerations and provide an online tool to aid in designing RbG studies.
- Laura J. Corbin
- , Vanessa Y. Tan
- & Nicholas J. Timpson
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Article
| Open AccessIdentification of genetic elements in metabolism by high-throughput mouse phenotyping
The genetic basis of metabolic diseases is incompletely understood. Here, by high-throughput phenotyping of 2,016 knockout mouse strains, Rozman and colleagues identify candidate metabolic genes, many of which are associated with unexplored regulatory gene networks and metabolic traits in human GWAS.
- Jan Rozman
- , Birgit Rathkolb
- & Martin Hrabe de Angelis
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Article
| Open AccessInequality in genetic cancer risk suggests bad genes rather than bad luck
Cancer heritability estimates can be obtained via decomposing trait variance into genetic and other factors. Here, the authors obtain the distribution of absolute genetic risk for 15 common cancers, and they use a number of metrics to show that the genetic risk varies considerably across individuals.
- Mats Julius Stensrud
- & Morten Valberg
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Article
| Open AccessActivating de novo mutations in NFE2L2 encoding NRF2 cause a multisystem disorder
The NRF2 transcription factor regulates the response to stress in mammalian cells. Here, the authors show that activating mutations in NRF2, commonly found in cancer cells, are found in four patients with a multisystem disorder characterized by immunodeficiency and neurological symptoms.
- Peter Huppke
- , Susann Weissbach
- & Jutta Gärtner
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Article
| Open AccessA defect in myoblast fusion underlies Carey-Fineman-Ziter syndrome
During embryogenesis, the cytoplasmic protein Myomarker (MYMK) mediates muscle fibre formation by fusion of myoblasts. Here, the authors identify autosomal recessive mutations in MYMK that cause Carey-Fineman-Ziter syndrome in humans, and model the disease variants in zebrafish.
- Silvio Alessandro Di Gioia
- , Samantha Connors
- & Elizabeth C. Engle
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Article
| Open AccessEvidence for ACTN3 as a genetic modifier of Duchenne muscular dystrophy
Duchenne muscular dystrophy is a disease caused by a single gene, characterized by progressive muscle weakness, but is variable between patients partly due to interactions of other genes. Here, the authors show that a commonACTN3polymorphism can modify the clinical phenotype.
- Marshall W. Hogarth
- , Peter J. Houweling
- & Kathryn N. North
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Article
| Open AccessA large-scale genome-wide association and meta-analysis identified four novel susceptibility loci for leprosy
Previous studies have shown genetic associations between leprosy and 18 different genes/loci. Here, Wang and colleagues perform genome-wide association study in Han Chinese leprosy patients and describe four novel loci to be associated to the disease.
- Zhenzhen Wang
- , Yonghu Sun
- & Furen Zhang
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Article
| Open AccessChallenges and disparities in the application of personalized genomic medicine to populations with African ancestry
Personalized medicine requires accurate and ethnicity-optimized reference genome panels. Here, the Consortium on Asthma among African-ancestry Populations in the Americas (CAAPA) evaluates typical variant filters and existing genome databases against newly sequenced African-ancestry populations.
- Michael D. Kessler
- , Laura Yerges-Armstrong
- & Timothy D. O’Connor
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Article
| Open AccessMBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta
Osteogenesis imperfecta (OI) is genetically linked to autosomal dominant or autosomal recessive mutations. Here, Marini et al. describe two families with X-chromosome-linked OI with mutations in MBTPS2 that alter regulated intramembrane proteolysis and subsequent defects in collagen crosslinking and osteoblast function.
- Uschi Lindert
- , Wayne A. Cabral
- & Vorasuk Shotelersuk
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Article
| Open AccessGenome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA
Circulating metabolites reflect human health and disease. Here, Kettunen et al. perform a genome-wide association study on 123 circulating metabolic traits and identify novel genetic loci influencing systemic metabolism. They also link new molecular pathways with a known cardiovascular risk factor Lp(a).
- Johannes Kettunen
- , Ayşe Demirkan
- & Mika Ala-Korpela