Jerome I. Rotter

1 month ago | nature.com | Magdalena Sevilla-Gonzalez |Elizabeth Litkowski |Hyunkyung Kim |Ching-Ti Liu |Chenglong Yu |John McNeil | +12 more

AbstractElevated fasting insulin levels (FI), indicative of altered insulin secretion and sensitivity, may precede type 2 diabetes (T2D) and cardiovascular disease onset. In this study, we group FI-associated genetic variants based on their genetic and phenotypic similarities and identify seven clusters with distinct mechanisms contributing to elevated FI levels.

Jan 12, 2025 | nature.com | Virginia S. Hahn |Ruin Moaddel |Joel S. Bader |Robert Gerszten |Jerome I. Rotter |Stephen S. Rich | +4 more

AbstractPeople living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure.

May 6, 2024 | nature.com | Yash Pershad |Adrienne M. Stilp |Braxton D. Mitchell |Joshua Lewis |Nathalie Chami |Zhe Wang | +21 more

AbstractClonal hematopoiesis (CH) is characterized by the acquisition of a somatic mutation in a hematopoietic stem cell that results in a clonal expansion. These driver mutations can be single nucleotide variants in cancer driver genes or larger structural rearrangements called mosaic chromosomal alterations (mCAs). The factors that influence the variations in mCA fitness and ultimately result in different clonal expansion rates are not well understood.

Feb 19, 2024 | nature.com | Konstantinos Hatzikotoulas |Henry Taylor |Xianyong Yin |Kim Lorenz |Mark McCarthy |Anubha Mahajan | +6 more

AbstractType 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D.

Oct 30, 2023 | nature.com | Yasminka A. Jakubek |Adrienne M. Stilp |Justin Wong |Zuhal Özcan |Kathleen C. Barnes |Joshua C. Bis | +22 more

AbstractMegabase-scale mosaic chromosomal alterations (mCAs) in blood are prognostic markers for a host of human diseases. Here, to gain a better understanding of mCA rates in genetically diverse populations, we analyzed whole-genome sequencing data from 67,390 individuals from the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program.