Publications by authors named "Andrea Horimoto"

Article Synopsis
  • - The study investigates the genetic basis of Essential Hypertension (EH) in African-derived individuals from isolated quilombo populations in Brazil, focusing on 431 participants and using extensive genetic analysis techniques like SNP genotyping and local ancestry analysis.
  • - Linkage analysis revealed 22 regions of interest with significant gene associations, while fine-mapping identified 60 candidate genes related to EH, unveiling new genetic insights that could improve understanding and treatment of hypertension.
  • - The findings suggest potential targets for future research on hypertension, aiming to enhance personalized medical approaches and public health efforts for underrepresented African-derived populations, despite some limitations like restricted SNP coverage and reliance on self-reported data.
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Background: Chronic kidney disease (CKD) is highly prevalent in Central America, and genetic factors may contribute to CKD risk. To understand the influences of genetic admixture on CKD susceptibility, we conducted an admixture mapping screening of CKD traits and risk factors in US Hispanic and Latino individuals from Central America country of origin.

Methods: We analyzed 1023 participants of HCHS/SOL (Hispanic Community Health Study/Study of Latinos) who reported 4 grandparents originating from the same Central America country.

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Article Synopsis
  • Educational attainment is linked to cardiovascular health, and a large genomic study examined how it interacts with cholesterol and triglyceride levels in nearly 226,315 individuals across five population groups.
  • The study identified 18 new genetic variations related to lipid levels—nine for low-density lipoprotein (LDL), seven for high-density lipoprotein (HDL), and two for triglycerides (TG)—some of which interact with educational attainment.
  • Researchers also found five gene targets that potentially interact with FDA-approved drugs, suggesting a connection between genetics and drug responses related to lipid metabolism and overall health.
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Background: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear.

Objective: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort.

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Article Synopsis
  • This study explores how genetic variation and environmental factors influence metabolic pathways and disease risks in Hispanic/Latino individuals, particularly focusing on their distinct ancestries.
  • Researchers analyzed 640 metabolites in a large cohort, identifying significant associations between specific metabolites and ancestry-derived genomic regions using advanced mass spectrometry techniques.
  • Key discoveries include finding that Native American and African ancestry regions are linked to the quantity of certain metabolites, which could have implications for understanding common diseases affecting these populations.
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Alzheimer disease (AD) is the most common form of senile dementia, with high incidence late in life in many populations including Caribbean Hispanic (CH) populations. Such admixed populations, descended from more than one ancestral population, can present challenges for genetic studies, including limited sample sizes and unique analytical constraints. Therefore, CH populations and other admixed populations have not been well represented in studies of AD, and much of the genetic variation contributing to AD risk in these populations remains unknown.

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Sex differences in Parkinson Disease (PD) risk are well-known. However, it is still unclear the role of sex chromosomes in the development and progression of PD. We performed the first X-chromosome Wide Association Study (XWAS) for PD risk in Latin American individuals.

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Article Synopsis
  • Estimated glomerular filtration rate (eGFR) is a key metric for assessing kidney function and identifying chronic kidney disease (CKD), particularly among Hispanic/Latino populations, where disease prevalence can vary.
  • The study evaluates the effectiveness of polygenic risk scores (PRS) for eGFR prediction by comparing methods like clumping and thresholding (C&T) and PRS-CS using data from diverse ancestry groups in Hispanic/Latino individuals.
  • Results indicate that all eGFR PRSs were strongly linked to kidney function, with combined PRSs showing the highest accuracy in predicting lower risks of CKD, confirmed by replication in another dataset from the Women's Health Initiative.
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Article Synopsis
  • Previous Parkinson's disease genome-wide association studies (GWAS) focused mainly on individuals of European ancestry, resulting in polygenic risk scores (PRS) that may not accurately predict PD risk in non-European populations.
  • In this study, a PD PRS was developed specifically for a Latino cohort and validated using data from independent Latino subjects and additional Peruvian controls, which showed varying predictive strengths.
  • Findings indicate that while the PRS shows promise for predicting PD risk among Latinos, differences in genetic ancestry and the limitations of relying on European data highlight the need for more inclusive research to refine risk prediction across diverse populations.
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Hispanic/Latinos have been underrepresented in genome-wide association studies (GWAS) for anthropometric traits despite their notable anthropometric variability, ancestry proportions, and high burden of growth stunting and overweight/obesity. To address this knowledge gap, we analyzed densely imputed genetic data in a sample of Hispanic/Latino adults to identify and fine-map genetic variants associated with body mass index (BMI), height, and BMI-adjusted waist-to-hip ratio (WHRadjBMI). We conducted a GWAS of 18 studies/consortia as part of the Hispanic/Latino Anthropometry (HISLA) Consortium (stage 1, n = 59,771) and generalized our findings in 9 additional studies (stage 2, n = 10,538).

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Background And Aims: Common variants in fat mass and obesity-associated (FTO) gene have been implicated as a susceptibility locus for obesity and type 2 diabetes in different populations. Here, in an indigenous population-based study, we examined whether FTO rs9939609 has a role in susceptibility to glucose intolerance and obesity.

Methods: The study population comprised 949 full Xavante indigenous people (465 men) aged 18-99 years.

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Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups.

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Background: Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of CKD.

Methods: We performed genome-wide admixture mapping for both CKD and eGFR in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 Black participants from the Women's Health Initiative (WHI).

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It is well established that the oldest chronotype questionnaire, the morningness-eveningness questionnaire (MEQ), has significant heritability, and several associations have been reported between MEQ score and polymorphisms in candidate clock genes, a number of them reproducibly across populations. By contrast, there are no reports of heritability and genetic associations for the Munich chronotype questionnaire (MCTQ). Recent genome-wide association studies (GWAS) from large cohorts have reported multiple associations with chronotype as assessed by a single self-evaluation question.

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Objective: This work was undertaken in order to identify Parkinson's disease (PD) risk variants in a Latino cohort, to describe the overlap in the genetic architecture of PD in Latinos compared to European-ancestry subjects, and to increase the diversity in PD genome-wide association (GWAS) data.

Methods: We genotyped and imputed 1,497 PD cases and controls recruited from nine clinical sites across South America. We performed a GWAS using logistic mixed models; variants with a p-value <1 × 10 were tested in a replication cohort of 1,234 self-reported Latino PD cases and 439,522 Latino controls from 23andMe, Inc.

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Background: Genetic studies have primarily been conducted in European ancestry populations, identifying dozens of loci associated with late-onset Alzheimer's disease (AD). However, much of AD's heritability remains unexplained; as the prevalence of AD varies across populations, the genetic architecture of the disease may also vary by population with the presence of novel variants or loci.

Methods: We conducted genome-wide analyses of AD in a sample of 2565 Caribbean Hispanics to better understand the genetic contribution to AD in this population.

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Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P < 5 × 10), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P < 5 × 10).

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Article Synopsis
  • - The study focuses on understanding the genetic factors associated with Parkinson's disease (PD) in Latino populations, as previous research has primarily centered on European genetic backgrounds.
  • - It analyzed genome-wide data from 747 PD patients and 632 controls, revealing that PD patients had a higher prevalence of copy number variants linked to known PD genes, with the strongest association found in the PRKN gene.
  • - Notably, 5.6% of patients with early-onset PD carried a variant in PRKN, suggesting that while the overall burden of copy number variants was similar, those with genetic variants in key genes experienced earlier onset of the disease.
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Many factors influence the incidence of type 2 diabetes mellitus (T2DM). Here, we investigated the associations between socio-demographic characteristics and familial history with the 5-year incidence of T2DM in a family-based study conducted in Brazil. T2DM was defined as baseline fasting blood glucose ≥ 126 mg/dL or the use of any hypoglycaemic drug.

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Introduction: The engagement in sports or habitual physical activity (PA) has shown an extensive protective role against multiple diseases such as cancer, obesity, and many others. Additionally, PA has also a significant impact on life quality, since it aids with managing stress, preserving cognitive function and memory, and preventing fractures in the elderly.

Objective: Considering there has been multiple evidence showing that genetic variation underpins variation of PA-related traits, we aimed to estimate the heritability (h2) of these phenotypes in a sample from the Brazilian population and assess whether males and females differ in relation to those estimates.

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Resistant hypertension (RH) is defined as uncontrolled blood pressure despite treatment with three or more antihypertensive medications, including, if tolerated, a diuretic in adequate doses. It has been widely known that race is associated with blood pressure control. However, intense debate persists as to whether this is solely explained by unadjusted socioeconomical variables or genetic variation.

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Article Synopsis
  • Dysglycaemia refers to high blood glucose levels, which can lead to prediabetes and diabetes, and is associated with increased cardiovascular risks, prompting the study of its incidence and cardiometabolic risk factors over five years in a normoglycaemic sample.
  • The analysis used data from the Baependi Heart Study, excluding individuals already diagnosed with diabetes or those on diabetes medications, and employed mixed-effects logistic regression to explore relationships between dysglycaemia and risk factors.
  • The study found a 12.8% incidence of prediabetic dysglycaemia after five years, with waist circumference, systolic blood pressure, HDL cholesterol, and age being significant factors, while differences between sexes were noted in specific cardi
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Article Synopsis
  • Short and long sleep durations are linked to negative lipid profiles through different biological processes, which can affect levels of HDL, LDL, and triglycerides.* -
  • A study with 126,926 participants from diverse ancestries identified 49 new gene variants related to lipid levels influenced by sleep duration, as well as 10 additional variants specifically in European ancestry cohorts.* -
  • The research highlights important gene-sleep interactions that could explain variations in triglyceride levels, enhancing our knowledge of how sleep affects lipid metabolism.*
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