Journal article

Identifying the Lipidomic Effects of a Rare Loss-of-Function Deletion in ANGPTL3

Nicholas B Blackburn, Peter J Meikle, Juan M Peralta, Satish Kumar, Ana C Leandro, Melissa A Bellinger, Corey Giles, Kevin Huynh, Michael C Mahaney, Harald HH Goring, John L VandeBerg, Sarah Williams-Blangero, David C Glahn, Ravindranath Duggirala, John Blangero, Laura F Michael, Joanne E Curran



BACKGROUND: The identification and understanding of therapeutic targets for atherosclerotic cardiovascular disease is of fundamental importance given its global health and economic burden. Inhibition of ANGPTL3 (angiopoietin-like 3) has demonstrated a cardioprotective effect, showing promise for atherosclerotic cardiovascular disease treatment, and is currently the focus of ongoing clinical trials. Here, we assessed the genetic basis of variation in ANGPTL3 levels in the San Antonio Family Heart Study. METHODS: We assayed ANGPTL3 protein levels in ≈1000 Mexican Americans from extended pedigrees. By drawing upon existing plasma lipidome profiles and genomic data we conducted analyses to under..

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Awarded by National Institutes of Health (NIH)

Awarded by T2D-GENES Consortium

Awarded by NIH

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

This work was supported in part by National Institutes of Health (NIH) grants P01 HL045522 (SAFHS [San Antonio Family Heart Study] data collection), R01 HL113323 (whole-genome sequencing and genotyping), R01 HL140681 (lipid and cardiovascular disease [CVD] analysis), R37 MH059490 (analytical methods and software used), R01 EB015611 (analytical methods and software used), and T2D-GENES Consortium grants (U01 DK085524 [San Antonio Mexican American Family Studies], U01 DK085584, U01 DK085501, U01 DK085526, and U01 DK085545 [whole-genome sequencing]). This work was conducted, in part, in facilities constructed under the support of NIH grant C06 RR020547. Dr Meikle is supported by a senior research fellowship from the National Health and Medical Research Council of Australia (APP1042095). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.