Genome-wide characterization ofcirculating metabolic biomarkers

Publication: Nature

Minna K. Karjalainen, Savita Karthikeyan, Clare Oliver-Williams, Eeva Sliz, Elias Allara, Wing Tung Fung, Praveen Surendran, Weihua Zhang, Pekka Jousilahti, Kati Kristiansson, Veikko Salomaa, Matt Goodwin, David A. Hughes, Michael Boehnke, Lilian Fernandes Silva, Xianyong Yin, Anubha Mahajan, Matt J. Neville, Natalie R. van Zuydam, Renée de Mutsert, Ruifang Li-Gao, Dennis O. Mook-Kanamori, Ayse Demirkan, Jun Liu, China Kadoorie Biobank Collaborative Group, Estonian Biobank Research Team, FinnGen, …Johannes Kettunen

6 March 2024

Summary

Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases. Researchers present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. 

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Genetics of circulating inflammatory proteins identifies drivers of immune-mediated disease risk and therapeutic targets

Publication: Nature Immunology

Jing Hua Zhao, David Stacey, Niclas Eriksson, Erin Macdonald-Dunlop, Asa K Hedman et al

18 July 2023


Aberrant inflammatory responses play a role in pathogenesis of many diseases, including autoimmune conditions, cardiovascular diseases and cancers. In this study of genetic influences on inflammation-related proteins, an international team conducted a genome-wide association study of 91 plasma proteins in ~15,000 participants within the SCALLOP Consortium.

Having identified 180 gene-protein associations, they integrated with gene expression and disease genetics to provide insights into disease aetiology, implicating FGF5 in hypertension and cardiovascular disease, and lymphotoxin-α in multiple sclerosis.

The team identified both shared and distinct effects of specific proteins across immune mediated diseases, including directionally discordant functions for CD40 in rheumatoid arthritis versus multiple sclerosis and inflammatory bowel disease, and a role for CXCL5 in the aetiology of ulcerative colitis UC but not Crohns disease.

These results provide a powerful resource to understand the role of chronic inflammation in a wide range of diseases and facilitate future drug target prioritisation.

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Substantial somatic genomic variation and selection for BCOR mutations in human induced pluripotent stem cells

Publication: Nature Genetics

Foad J. Rouhani, Xueqing Zou, Petr Danecek, Cherif Badja, Tauanne Dias Amarante, Gene Koh, Qianxin Wu, Yasin Memari, Richard Durbin, Inigo Martincorena, Andrew R. Bassett, Daniel Gaffney & Serena Nik-Zainal

11 August 2022


Summary

DNA damage caused by factors such as ultraviolet radiation affect nearly three-quarters of all stem cell lines derived from human skin cells, say Cambridge researchers, who argue that whole genome sequencing is essential for confirming if cell lines are usable. Read the full news story.

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Refinements and considerations for trio whole-genome sequence analysis when investigating Mendelian diseases presenting in early childhood

Publication: HGG Advances

Courtney E. French, Helen Dolling, Karyn Mégy, Alba Sanchis-Juan, Ajay Kumar, Isabelle Delon, Matthew Wakeling, Lucy Mallin, Shruti, Agrawal, Topun Austin, Florence Walston, Soo-Mi Park, Alasdair, Parker, Chinthika Piyasena, Kimberley Bradbury, Sian Ellard, David H.Rowitch, LucyRaymond

24 May 2022


Summary

More than a third of severely sick babies referred for rapid whole genome sequencing received a vital genetic diagnosis. Results from the latest Cambridge genomic study supported by NIHR Cambridge BRC and NIHR BioResource, confirm rapid whole genome sequencing (WGS) as an effective early test to aid diagnosis in severely ill children. Read the full story. 

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The NHS England 100,000 Genomes Project – Feasibility and utility of centralised genome sequencing for children with cancer

Publication: British Journal of Cancer

Jamie Trotman, Ruth Armstrong, Helen Firth, Claire Trayers, James Watkins, Kieren Allinson, James C. Nicholson, G. A. Amos Burke, Sam Behjati, Matthew J. Murray, Catherine E. Hook, Patrick Tarpey

22 April 2022


Summary

As part of the national 100,000 Genome Project, researchers recruited from 36 children, across 23 different solid tumour types. Whole genome sequencing (WGS) data from paired tumour (fresh-frozen tissue) and matched normal (blood) samples was analysed.  The results for each case were clinically reviewed at the Cambridge paediatric oncology Genomic Tumour Advisory Board (GTAB), and formal report of the results was written.

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A systematic CRISPR screen defines mutational mechanisms underpinning signatures caused by replication errors and endogenous DNA damage

Publication: Nature Cancer

Xueqing Zou, Gene Ching Chiek Koh, Arjun Scott Nanda, Andrea Degasperi, Katie Urgo, Theodoros I. Roumeliotis, Chukwuma A. Agu, Cherif Badja, Sophie Momen, Jamie Young, Tauanne Dias Amarante, Lucy Side, Glen Brice, Vanesa Perez-Alonso, Daniel Rueda, Celine Gomez, Wendy Bushell, Rebecca Harris, Jyoti S. Choudhary, Genomics England Research Consortium, Josef Jiricny,
William C. Skarnes & Serena Nik-Zainal

26 April 2021


Summary

A new way to identify tumours that could be sensitive to particular immunotherapies has been developed using data from thousands of NHS cancer patient samples sequenced through the 100,000 Genomes Project.  The MMRDetect clinical algorithm makes it possible to identify tumours that have ‘mismatch repair deficiencies’ and then improve the personalisation of cancer therapies to exploit those weaknesses.

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