Browsing by Author "Walker R"

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    Associations between maternal stressful life events and child health outcomes in indigenous and non-indigenous groups in New Zealand
    (Taylor and Francis Group, 2023-12-13) Paine S-J; Walker R; Lee A; Loring B; Signal TL
    Exposure to stressful life events (SLE) around the time of pregnancy is associated with adverse health outcomes for mothers and children. Previous New Zealand research found Indigenous Māori women are more likely to be exposed to SLE than non-Māori, and are exposed to a higher number of SLE. The consequences of this for ethnic inequities in child health outcomes are unknown. This paper examines the relationship between patterns of maternal SLE exposure with child health and development outcomes at age 3 years, for Indigenous and non-Indigenous children. We found most children had a stressful early life environment at least sometimes, but more than a quarter of Māori children had a mother experiencing multiple SLE on all occasions measured. We found a clear association between maternal experiences of SLE and disordered child sleep and development concerns. While not able to fully assess the contribution of maternal SLE to ethnic inequities in child health outcomes, we did clearly demonstrate that more Māori children have mothers exposed to multiple SLE, and that these maternal SLE are associated with poorer child outcomes. The impacts of chronic SLE exposure need to be better understood, especially given the large ethnic disparity in chronic SLE exposure.
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    Identifying colorectal cancer caused by biallelic MUTYH pathogenic variants using tumor mutational signatures
    (Springer Nature Limited, 6/06/2022) Georgeson P; Harrison TA; Pope BJ; Zaidi SH; Qu C; Steinfelder RS; Lin Y; Joo JE; Mahmood K; Clendenning M; Walker R; Amitay EL; Berndt SI; Brenner H; Campbell PT; Cao Y; Chan AT; Chang-Claude J; Doheny KF; Drew DA; Figueiredo JC; French AJ; Gallinger S; Giannakis M; Giles GG; Gsur A; Gunter MJ; Hoffmeister M; Hsu L; Huang W-Y; Limburg P; Manson JE; Moreno V; Nassir R; Nowak JA; Obón-Santacana M; Ogino S; Phipps AI; Potter JD; Schoen RE; Sun W; Toland AE; Trinh QM; Ugai T; Macrae FA; Rosty C; Hudson TJ; Jenkins MA; Thibodeau SN; Winship IM; Peters U; Buchanan DD
    Carriers of germline biallelic pathogenic variants in the MUTYH gene have a high risk of colorectal cancer. We test 5649 colorectal cancers to evaluate the discriminatory potential of a tumor mutational signature specific to MUTYH for identifying biallelic carriers and classifying variants of uncertain clinical significance (VUS). Using a tumor and matched germline targeted multi-gene panel approach, our classifier identifies all biallelic MUTYH carriers and all known non-carriers in an independent test set of 3019 colorectal cancers (accuracy = 100% (95% confidence interval 99.87-100%)). All monoallelic MUTYH carriers are classified with the non-MUTYH carriers. The classifier provides evidence for a pathogenic classification for two VUS and a benign classification for five VUS. Somatic hotspot mutations KRAS p.G12C and PIK3CA p.Q546K are associated with colorectal cancers from biallelic MUTYH carriers compared with non-carriers (p = 2 × 10-23 and p = 6 × 10-11, respectively). Here, we demonstrate the potential application of mutational signatures to tumor sequencing workflows to improve the identification of biallelic MUTYH carriers.