@article{95df3a4df2d9468086d264f0b0365012,
title = "Exome sequence association study of levels and longitudinal change of cardiovascular risk factor phenotypes in European Americans and African Americans from the Atherosclerosis Risk in Communities Study",
abstract = "Cardiovascular disease (CVD) is responsible for 31% of all deaths worldwide. Among CVD risk factors are age, race, increased systolic blood pressure (BP), and dyslipidemia. Both BP and blood lipids levels change with age, with a dose-dependent relationship between the cumulative exposure to hyperlipidemia and the risk of CVD. We performed an exome sequence association study using longitudinal data with up to 7805 European Americans (EAs) and 3171 African Americans (AAs) from the Atherosclerosis Risk in Communities (ARIC) study. We assessed associations of common (minor allele frequency > 5%) nonsynonymous and splice-site variants and gene-based sets of rare variants with levels and with longitudinal change of seven CVD risk factor phenotypes (BP traits: systolic BP, diastolic BP, pulse pressure; lipids traits: triglycerides, total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C]). Furthermore, we investigated the relationship of the identified variants and genes with select CVD endpoints. We identified two novel genes: DCLK3 associated with the change of HDL-C levels in AAs and RAB7L1 associated with the change of LDL-C levels in EAs. RAB7L1 is further associated with an increased risk of heart failure in ARIC EAs. Investigation of the contribution of genetic factors to the longitudinal change of CVD risk factor phenotypes promotes our understanding of the etiology of CVD outcomes, stressing the importance of incorporating the longitudinal structure of the cohort data in future analyses.",
keywords = "exome sequencing, lipids, longitudinal analysis",
author = "Feofanova, {Elena V.} and Elise Lim and Han Chen and Lee, {Min Jae} and Liu, {Ching Ti} and Cupples, {L. Adrienne} and Eric Boerwinkle",
note = "Funding Information: The authors thank the staff and participants of the ARIC and FOS study for their important contributions. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I). Funding support for “Building on GWAS for NHLBI‐diseases: the U.S. CHARGE consortium” was provided by the NIH through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Sequencing was carried out at the Baylor College of Medicine Human Genome Sequencing Center (U54HG003273 and R01HL086694). The Framingham Offspring Study is supported by NIH NHLBI Framingham Heart Study contracts N01‐HC‐25195, HHSN268201500001I, and 75N92019D00031. Genotyping, quality control, and calling of the Illumina HumanExome BeadChip in the Framingham Heart Study were supported by funding from the National Heart, Lung, and Blood Institute Division of Intramural Research (Daniel Levy and Christopher J. O'Donnell, Principle Investigators). Support for the centralized genotype calling was provided by Building on GWAS for NHLBI diseases: the U.S. CHARGE consortium through the National Institutes of Health (NIH) American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Funding Information: The authors thank the staff and participants of the ARIC and FOS study for their important contributions. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services (contract numbers HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I). Funding support for “Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium” was provided by the NIH through the American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Sequencing was carried out at the Baylor College of Medicine Human Genome Sequencing Center (U54HG003273 and R01HL086694). The Framingham Offspring Study is supported by NIH NHLBI Framingham Heart Study contracts N01-HC-25195, HHSN268201500001I, and 75N92019D00031. Genotyping, quality control, and calling of the Illumina HumanExome BeadChip in the Framingham Heart Study were supported by funding from the National Heart, Lung, and Blood Institute Division of Intramural Research (Daniel Levy and Christopher J. O'Donnell, Principle Investigators). Support for the centralized genotype calling was provided by Building on GWAS for NHLBI diseases: the U.S. CHARGE consortium through the National Institutes of Health (NIH) American Recovery and Reinvestment Act of 2009 (5RC2HL102419). Publisher Copyright: {\textcopyright} 2021 Wiley Periodicals LLC",
year = "2021",
month = sep,
doi = "10.1002/gepi.22390",
language = "English (US)",
volume = "45",
pages = "651--663",
journal = "Genetic Epidemiology",
issn = "0741-0395",
publisher = "Wiley-Liss Inc.",
number = "6",
}