Konrad J Karczewski

Jul 3, 2024 | nature.com | Caitlin Carey |Robbee Wedow |Duncan Palmer |Masahiro Kanai |Konrad J Karczewski |Samuel Bryant | +6 more

AbstractData within biobanks capture broad yet detailed indices of human variation, but biobank-wide insights can be difficult to extract due to complexity and scale. Here, using large-scale factor analysis, we distill hundreds of variables (diagnoses, assessments and survey items) into 35 latent constructs, using data from unrelated individuals with predominantly estimated European genetic ancestry in UK Biobank.

Jun 3, 2024 | nature.com | Rahul Gupta |Masahiro Kanai |Timothy Durham |Anna V. Kotrys |Wei Zhou |Konrad J Karczewski | +1 more

Correction to: Nature https://doi.org/10.1038/s41586-023-06426-5Published online 16 August 2023When performing a genome-wide association study (GWAS), the choice of which allele (reference vs. alternate) is considered the “effect allele” is arbitrary. In our computations, we chose the reference allele. For a small subset of our results, the effect sizes were erroneously attributed to the alternate allele.

Mar 15, 2024 | medrxiv.org | Konrad J Karczewski |Rahul Gupta |Masahiro Kanai |Wenhan Lu

K.J.K. is a consultant for Tome Biosciences, AlloDx, and Vor Biosciences, and a member of the scientific advisory board of Nurture Genomics. M.J.D is a founder of Maze Therapeutics. B.M.N. is a member of the scientific advisory board at Deep Genomics and Neumora. This work was supported by the Novo Nordisk Foundation (NNF21SA0072102), NIH grants R37MH107649, R00MH117229, K01MH121659, F31HL167378, and F30AG074507, and BroadIgnite funding.

Dec 6, 2023 | nature.com | Laurent C. Francioli |Sarah Stenton |Samantha Baxter |Benjamin M. Neale |Joel N. Hirschhorn |Heidi Rehm | +3 more

AbstractRecessive diseases arise when both copies of a gene are impacted by a damaging genetic variant. When a patient carries two potentially causal variants in a gene, accurate diagnosis requires determining that these variants occur on different copies of the chromosome (that is, are in trans) rather than on the same copy (that is, in cis). However, current approaches for determining phase, beyond parental testing, are limited in clinical settings.

Aug 16, 2023 | nature.com | Rahul Gupta |Masahiro Kanai |Timothy Durham |Anna V. Kotrys |Wei Zhou |Konrad J Karczewski | +1 more

AbstractMitochondrial DNA (mtDNA) is a maternally inherited, high-copy-number genome required for oxidative phosphorylation1. Heteroplasmy refers to the presence of a mixture of mtDNA alleles in an individual and has been associated with disease and ageing. Mechanisms underlying common variation in human heteroplasmy, and the influence of the nuclear genome on this variation, remain insufficiently explored.