Simin Liu

Simin Liu
Brown University · Department of Epidemiology

MD, ScD

About

655
Publications
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Introduction

Publications

Publications (655)
Article
Full-text available
The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome arrays, resulting in over 100 associated variants. We extended this work with high-coverage whole genome sequencing analyses from fifteen cohorts in NHLBI’s Trans-Omics for Precision Medicine (TOPMed) program. Over 23,000 non-diabetic i...
Article
Full-text available
Objective: Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. Research design and methods: We included 108,681 postmenopausal women without T2D at baseline...
Article
OBJECTIVE Whether and how dietary protein intake is linked to type 2 diabetes (T2D) remains unclear. The aim of this study was to investigate the associations of protein intake with development of T2D and the potential mediating roles of T2D biomarkers. RESEARCH DESIGN AND METHODS We included 108,681 postmenopausal women without T2D at baseline fr...
Article
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In a multi-stage analysis of 52,436 individuals aged 17-90 across diverse cohorts and biobanks, we train, test, and evaluate a polygenic risk score (PRS) for hypertension risk and progression. The PRS is trained using genome-wide association studies (GWAS) for systolic, diastolic blood pressure, and hypertension, respectively. For each trait, PRS i...
Article
Studies have suggested that adults with gallbladder disease have increased risk of type 2 diabetes. This prospective cohort study assesses the risk of type 2 diabetes in postmenopausal women with gallbladder disease. Data from women aged 50-79 years (Mean 63.2, SD 7.2) enrolled in the Women’s Health Initiative from 1993 to 2005 was analyzed. Cox pr...
Article
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Background The associations of red and processed meat with chronic disease risk remains unsettled, in part because of measurement error in self-reported diet. Objectives To develop metabolomics-based biomarkers for red and processed meat, and to associate biomarker-calibrated meat intake with chronic disease risk among postmenopausal women. Desig...
Article
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Aims/hypothesis Type 2 diabetes is a growing global public health challenge. Investigating quantitative traits, including fasting glucose, fasting insulin and HbA1c, that serve as early markers of type 2 diabetes progression may lead to a deeper understanding of the genetic aetiology of type 2 diabetes development. Previous genome-wide association...
Article
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Analyses of data from genome-wide association studies on unrelated individuals have shown that, for human traits and diseases, approximately one-third to two-thirds of heritability is captured by common SNPs. However, it is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular...
Article
Background: Diabesity defines the concurrent manifestation of type 2 diabetes (T2D) and obesity (BMI≥30 kg/m ² ) in the development of cardiovascular diseases, although the genetic basis for this joint phenotype remain poorly understood. Objective: This study aimed to identify the overlapping genetic patterns for diabesity incidence in 3,231 self-r...
Article
Background: To investigate the association between walking pace and the risk of heart failure (HF) and HF sub-types. Methods: We examined associations of self-reported walking pace with risk of incident HF and HF subtypes of preserved (HFpEF) and reduced (HFrEF) ejection fractions, among 25,183 postmenopausal women, ages 50-79 years. At enrollme...
Article
Genetic studies on telomere length are important for understanding age-related diseases. Prior GWASs for leukocyte TL have been limited to European and Asian populations. Here, we report the first sequencing-based association study for TL across ancestrally diverse individuals (European, African, Asian, and Hispanic/Latino) from the NHLBI Trans-Omi...
Article
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Importance Some prior evidence suggests that adverse pregnancy outcomes (APOs) may be associated with heart failure (HF). Identifying unique factors associated with the risk of HF and studying HF subtypes are important next steps. Objective To investigate the association of APOs with incident HF overall and stratified by HF subtype (preserved vs r...
Article
Background: Early-life exposures play key roles in the development of metabolic diseases. Whether such effects exist beyond one generation remains unclear. This study aimed to determine the transgenerational association of early-life exposure to the Chinese famine of 1959 to 1962 with the trajectories of body mass index (BMI), waist circumference...
Article
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Background The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship wi...
Preprint
The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121...
Article
Background and Purpose Stroke is the leading cause of death and long-term disability worldwide. Previous genome-wide association studies identified 51 loci associated with stroke (mostly ischemic) and its subtypes among predominantly European populations. Using whole-genome sequencing in ancestrally diverse populations from the Trans-Omics for Prec...
Preprint
Full-text available
Background: We used summary statistics from previously-published GWAS of systolic and diastolic BP and of hypertension to construct Polygenic Risk Scores (PRS) to predict hypertension across diverse populations. Methods: We used 10,314 participants of diverse ancestry from BioMe to train trait-specific PRS. We implemented a novel approach to select...
Article
An increasing body of evidence implicates high levels of selenium intake in the development of diabetes, although prospective studies remain sparse. We conducted a nested case-control study of 622 diabetes incident cases and 622-age, sex, and follow-up time-matched controls in the prospective Jinchang cohort of 48,001 participants with a median of...
Article
Background Assessing estimated sodium (Na) and potassium (K) intakes derived from 24-h urinary excretions versus a spot urine sample if comparable could reduce participant burden in epidemiologic and clinical studies. Objectives In a two-week controlled feeding study, Na and K excretion from a 24-h urine collection were compared with a first void...
Article
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Background The plant‐based Dietary Portfolio combines established cholesterol‐lowering foods (plant protein, nuts, viscous fiber, and phytosterols), plus monounsaturated fat, and has been shown to improve low‐density lipoprotein cholesterol and other cardiovascular disease (CVD) risk factors. No studies have evaluated the relation of the Dietary Po...
Article
The potential role of nutritional factors in the development of peripheral arterial disease (PAD) remains poorly understood. We evaluated multiple recommended eating patterns as reflected by predefined diet quality indices in relation to long-term risk of PAD. We included 138 506 US postmenopausal women in the Women’s Health Initiative who had no k...
Poster
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Objectives To assess the association of the plant-based cholesterol-lowering diet, the Portfolio Diet, with incident type 2 diabetes in women. Methods We followed 147,732 postmenopausal women initially free of diabetes in the Women's Health Initiative (WHI) Clinical Trials and Observational Study from 1993 through 2017. Adherence to the Portfolio...
Article
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The clinical evidence indicates the compromised application of titanium implants (TI) in diabetics, associated with reactive oxygen species (ROS) overproduction at the bone-implant interface. Silk fibroin has exerted impressive biocompatibility in application of biomedical material and optimal anti-diabetic effect as oriental medicine. We proposed...
Article
Background Recent experimental work has shown that phthalates may increase inflammation. Prior research has not examined the role of exposure to phthalates in relation to inflammatory status among postmenopausal women who are at higher risk of developing inflammation-related chronic disorders. Objectives We aimed to examine the associations of uri...
Article
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Objective To evaluate the association between pasta meal intake and long-term risk of developing diabetes or atherosclerotic cardiovascular disease (ASCVD, including coronary heart disease (CHD) and stroke) in postmenopausal women. Design Prospective cohort study. Setting Women’s Health Initiative (WHI) in the USA. Participants 84 555 postmenopaus...
Article
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Background: Pancreatic cancer risk is increasing in countries with high consumption of Western dietary patterns and rising obesity rates. We examined the hypothesis that specific dietary patterns reflecting hyperinsulinemia (empirical dietary index for hyperinsulinemia-EDIH), systemic inflammation (empirical dietary inflammatory pattern-EDIP), and...
Article
Background The cholesterol content of circulating triglyceride-rich lipoproteins is characterized as remnant cholesterol, although little is known about its role in the development of CVD outcomes, all-cause mortality, or transplant failure in kidney transplant recipients. Our primary aim was to investigate the prospective association of remnant ch...
Article
Full-text available
Genomic discovery and characterization of risk loci for type 2 diabetes (T2D) have been conducted primarily in individuals of European ancestry. We conducted a multiethnic genome-wide association study of T2D among 53,102 cases and 193,679 controls from African, Hispanic, Asian, Native Hawaiian, and European population groups in the Population Arch...
Article
Abstract OBJECTIVE The empirical dietary index for hyperinsulinemia (EDIH) and empirical dietary inflammatory pattern (EDIP) scores assess the insulinemic and inflammatory potentials of habitual dietary patterns, irrespective of the macronutrient content, and are based on plasma insulin response or inflammatory biomarkers, respectively. The glycemi...
Preprint
The genetic determinants of fasting glucose (FG) and fasting insulin (FI) have been studied mostly through genome and exome arrays, resulting in over 100 associated variants. We extended this work with a high-coverage whole genome sequencing (WGS) analysis from fifteen cohorts in the NHLBI Trans-Omics for Precision Medicine (TOPMed) program. More t...
Preprint
Full-text available
Type 2 diabetes is increasing in all ancestry groups ¹ . Part of its genetic basis may reside among the rare (minor allele frequency <0.1%) variants that make up the vast majority of human genetic variation ² . We analyzed high-coverage (mean depth 38.2x) whole genome sequencing from 9,639 individuals with T2D and 34,994 controls in the NHLBI’s Tra...
Article
Background: Cardiometabolic abnormalities are a leading cause of death among women, including women with cancer. Methods: This study examined the association between prediagnosis cardiovascular health and total and cause-specific mortality among 12,076 postmenopausal women who developed local- or regional-stage invasive cancer in the Women's Hea...
Article
Objective: To determine if premature menopause and early menarche are associated with increased risk of AAA, and to explore potential effect modification by smoking history. Summary of Background Data: Despite worse outcomes for women with AAA, no studies have prospectively examined sex-specific risk factors, such as premature menopause and earl...
Article
Background - In the Women's Health Initiative hormone therapy (WHI-HT) trials, treatment with oral conjugated equine estrogens and medroxyprogesterone acetate (CEE+MPA) resulted in increased risk of coronary heart disease (CHD), while oral conjugated equine estrogens alone (CEE) did not. Methods - 481 metabolites were measured at baseline and at 1-...
Article
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Background: Most studies that analyze the association between serum folate levels and cognitive function either restrict their assessments to specific clinical scenarios or do not include middle-aged individuals, to whom strategies for preventing cognitive impairment may be more feasible. Objective: To examine the association between serum folate...
Article
Introduction: Recent studies suggest that both sex-specific genetic risk factors and those shared between dementia and stroke are involved in dementia pathogenesis. Methods: We performed both single-variant and gene-based genome-wide association studies of >11,000 whole genome sequences from the Women's Health Initiative cohort to discover loci...
Article
Background: Choline plays an integral role in one-carbon metabolism in the body, but it is unclear whether genetic polymorphisms are associated with variations in plasma choline and its metabolites. Objectives: This study aimed to evaluate the association of genetic variants in choline and one-carbon metabolism with plasma choline and its metabo...
Chapter
Cardiometabolic diseases, including obesity, type 2 diabetes, and a variety of cardiovascular diseases constitute a global pandemic. The prevalence of cardiometabolic diseases and associated medical costs have increased dramatically in recent years, bringing greater health care burden to communities, families, and individuals. Therefore, identifyin...
Article
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Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-ca...
Article
Objective Few studies have prospectively examined associations of lipoprotein(a) [Lp(a)] levels with risk of abdominal aortic aneurysm (AAA), particularly in women. Accounting for commonly recognized risk factors, we investigated baseline Lp(a) levels with risk of AAA among postmenopausal women participating in the ongoing national Women’s Health I...
Article
Background: The Western dietary pattern (WD) is positively associated with risk of coronary artery disease (CAD) and cancer, whereas the Prudent dietary pattern (PD) may be protective. Foods may influence metabolite concentrations as well as oxidative stress and lipid dysregulation, biological mechanisms associated with CAD and cancer. Objective:...
Article
Objective: We studied associations between social support, social network size, social strain, or stressful life events and risk of coronary heart disease (CHD) in postmenopausal women with type 2 diabetes. Research design and methods: From the Women's Health Initiative, 5,262 postmenopausal women with type 2 diabetes at baseline were included....
Article
Full-text available
Objectives We aimed to evaluate diet quality as reflected by multiple a priori dietary pattern indices in relation to incident PAD. Methods We included 138,506 US postmenopausal women aged 50–79 years without known PAD at baseline (1993–1998) of the Women's Health Initiative. Score of 4 dietary pattern indices, including the alternate Mediterranea...
Article
Full-text available
Objectives Dietary patterns that promote chronic systemic inflammation, hyperinsulinemia, or hyperglycemia may influence type 2 diabetes (T2D) risk. We evaluated an empirical dietary index for hyperinsulinemia (EDIH), empirical dietary inflammatory pattern (EDIP), glycemic index (GI), and glycemic load (GL), and risk of T2D among US postmenopausal...
Article
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Background Familial dysalbuminemic hyperthyroxinemia (FDH) is a rare autosomal dominant disorder whose clinical characteristics remain incompletely understood, we investigated the role of albumin gene mutation in relation to miscarriage rate in a large pedigree of FDH followed up for four years. Patients and Methods The proband and extended family...
Article
OBJECTIVE To examine the association between manganese intake and the risk of type 2 diabetes in postmenopausal women and determine whether this association is mediated by circulating markers of inflammation. RESEARCH DESIGN AND METHODS We included 84,285 postmenopausal women without a history of diabetes from the national Women’s Health Initiativ...
Article
Background Women represent a large proportion of the growing heart failure ( HF ) epidemic, yet data are lacking regarding optimal dietary and lifestyle prevention strategies for them. Specifically, the association between magnesium intake and HF in a multiracial cohort of women is uncertain. Methods and Results We included 97 725 postmenopausal w...
Article
Full-text available
Objective To examine the associations of dietary and supplemental magnesium (Mg) as assessed by a semi-quantitative food frequency questionnaire with cognitive outcomes among ageing women. Design This work conducts a prospective cohort study of participants enrolled in the Women’s Health Initiative Memory Study (WHIMS), which was subsequently exte...
Article
Background: Whether health outcomes of menopausal estrogen therapy differ between women with and without bilateral salpingo-oophorectomy (BSO) is unknown. Objective: To examine estrogen therapy outcomes by BSO status, with additional stratification by 10-year age groups. Design: Subgroup analyses of the randomized Women's Health Initiative Est...
Preprint
Full-text available
Introduction: Heart failure (HF) is understudied among women; especially, genomic evidence implicating shared or unique mechanisms of HF with respect to reduced or preserved ejection fraction (HFrEF, HFpEF) is lacking across ethnic populations of women. Prior genome-wide association studies (GWAS) have identified approximately 30 suggestive genetic...
Article
The anticarcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to 'stage migration', with users more likely diagnosed with early rather than late stage cancer. The association between prior statin use and colorectal cancer (CRC) stage at diagnosis in the Women's Health Initiative (WHI) was investigated. The study...
Article
Full-text available
While dietary factors are important modifiable risk factors for type 2 diabetes (T2D), the causal role of carbohydrate quality in nutrition remains controversial. Dietary glycemic index (GI) and glycemic load (GL) have been examined in relation to the risk of T2D in multiple prospective cohort studies. Previous meta-analyses indicate significant re...
Article
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Published meta-analyses indicate significant but inconsistent incident type-2 diabetes(T2D)-dietary glycemic index (GI) and glycemic load (GL) risk ratios or risk relations (RR). It is nowover a decade ago that a published meta-analysis used a predefined standard to identify validstudies. Considering valid studies only, and using random effects dos...
Article
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Objective: Both exposure to heavy metals and alcohol intake have been related to the risk of type 2 diabetes (T2D). In this study, we aimed to assess the potential interactions between metal exposure and alcohol intake on the risk of T2D and prediabetes in a cohort of Chinese male workers. Methods: We conducted a cross-sectional analysis of 26,0...
Article
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Background Recent evidence suggests that racial/ethnic differences in circulating levels of free or bioavailable 25‐hydroxy vitamin D (25[OH]D) rather than total 25(OH)D may explain apparent racial disparities in cardiovascular disease (CVD). We prospectively examined black‐white differences in the associations of total, free, and bioavailable 25(O...
Data
Table S1. HRs for MI Risk According to Total 25(OH)D and PTH Levels Among Postmenopausal Women Table S2. HRs for Stroke Risk According to Total 25(OH)D and PTH Levels Among Postmenopausal Women Table S3. HRs for CVD Mortality Risk According to Total 25(OH)D and PTH Levels Among Postmenopausal Women Figure S1. Vitamin D binding protein (VDBP). F...
Article
Polygenic risk scores (PRSs) are weighted sums of risk allele counts of single-nucleotide polymorphisms (SNPs) associated with a disease or trait. PRSs are typically constructed based on published results from Genome-Wide Association Studies (GWASs), and the majority of which has been performed in large populations of European ancestry (EA) individ...
Article
Background: Phthalates are ubiquitous endocrine disrupting chemicals present in a wide variety of consumer products. However, the personal characteristics associated with phthalate exposure are unclear. Objectives: We sought to describe personal, behavioral, and reproductive characteristics associated with phthalate metabolite concentrations in...
Article
Importance Atherosclerotic cardiovascular disease (ASCVD) kills approximately 1 in every 3 US women. Current cholesterol, hypertension, and aspirin guidelines recommend calculating 10-year risk of ASCVD using the 2013 Pooled Cohort Equations (PCE). However, numerous studies have reported apparent overestimation of risk with the PCE, and reasons for...
Article
Background: "T50," shortened transformation time from primary to secondary calciprotein particles may reflect deranged mineral metabolism predisposing to vascular calcification and cardiovascular disease (CVD). The glycoprotein fetuin-A is a major T50 determinant. Methods: The Folic Acid For Vascular Outcome Prevention In Transplantation (FAVORI...
Article
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Tantalum (Ta)-coated porous Ti-6A1-4V scaffolds have better bioactivity than Ti-6A1-4V scaffolds; however, their bioperformance as an artificial vertebral body (AVB) is unknown. In the present study, we combined a Ta-coated Ti-6A1-4V scaffold with rabbit bone marrow stromal cells (BMSCs) for tissue-engineered AVB (TEAVB) construction and evaluated...
Article
Full-text available
The inconsistent findings from epidemiologic studies relating total sugars (TS) consumption to cardiovascular disease (CVD) or type 2 diabetes (T2D) risk may be partly due to measurement error (ME) in self-reported intake. Using regression calibration equations developed based on the predictive biomarker for TS and recovery biomarker for energy, we...
Article
Statement of significance: The high failure rate of bone implants in diabetic patients causes patients terrible pain and limits the clinical application of implant materials. The mechanism underlying this phenomenon needs elucidation so that it would be possible to develop corresponding solutions. Our study demonstrated that the AGEs-related and N...
Article
The diabetes-related high failure risk for endosseous implants appeals efficacious methods to improve the osteointergration on bone-implant interface (BII). Poly (lactic-co-glycolic) acid (PLGA) is widely used in tissue engineering, but its effects on the BII in diabetes remain elusive. To clarify this issue, 3D-printed porous titanium implants (TI...