scholarly journals Genetic underpinnings of regional adiposity distribution in African Americans: Assessments from the Jackson Heart Study

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0255609
Author(s):  
Mohammad Y. Anwar ◽  
Laura M. Raffield ◽  
Leslie A. Lange ◽  
Adolfo Correa ◽  
Kira C. Taylor
Keyword(s):  
Waist Circumference ◽  
Genetic Variants ◽  
African Ancestry ◽  
Visceral Adiposity ◽  
European Ancestry ◽  
Risk Scores ◽  
Jackson Heart Study ◽  
Anthropometric Measures ◽  
Heart Study ◽  
Common Genetic Variants

Background African ancestry individuals with comparable overall anthropometric measures to Europeans have lower abdominal adiposity. To explore the genetic underpinning of different adiposity patterns, we investigated whether genetic risk scores for well-studied adiposity phenotypes like body mass index (BMI) and waist circumference (WC) also predict other, less commonly measured adiposity measures in 2420 African American individuals from the Jackson Heart Study. Methods Polygenic risk scores (PRS) were calculated using GWAS-significant variants extracted from published studies mostly representing European ancestry populations for BMI, waist-hip ratio (WHR) adjusted for BMI (WHRBMIadj), waist circumference adjusted for BMI (WCBMIadj), and body fat percentage (BF%). Associations between each PRS and adiposity measures including BF%, subcutaneous adiposity tissue (SAT), visceral adiposity tissue (VAT) and VAT:SAT ratio (VSR) were examined using multivariable linear regression, with or without BMI adjustment. Results In non-BMI adjusted models, all phenotype-PRS were found to be positive predictors of BF%, SAT and VAT. WHR-PRS was a positive predictor of VSR, but BF% and BMI-PRS were negative predictors of VSR. After adjusting for BMI, WHR-PRS remained a positive predictor of BF%, VAT and VSR but not SAT. WC-PRS was a positive predictor of SAT and VAT; BF%-PRS was a positive predictor of BF% and SAT only. Conclusion These analyses suggest that genetically driven increases in BF% strongly associate with subcutaneous rather than visceral adiposity and BF% is strongly associated with BMI but not central adiposity-associated genetic variants. How common genetic variants may contribute to observed differences in adiposity patterns between African and European ancestry individuals requires further study.

scholarly journals Genetic Underpinnings of Regional Adiposity Distribution in African Americans: Assessments from the Jackson Heart Study

2020 ◽  
Author(s):  
Mohammad Y. Anwar ◽  
Laura M. Raffield ◽  
Leslie A. Lange ◽  
Adolfo Correa ◽  
Kira C. Taylor
Keyword(s):  
African Ancestry ◽  
Visceral Adiposity ◽  
European Ancestry ◽  
Risk Scores ◽  
Central Adiposity ◽  
Jackson Heart Study ◽  
Fat Percentage ◽  
Anthropometric Measures ◽  
Heart Study ◽  
Subcutaneous Adiposity

AbstractBackgroundAfrican ancestry individuals with comparable overall anthropometric measures to Europeans have lower abdominal adiposity. To explore genetic underpinning of different adiposity patterns, we investigated if genetic risk scores for well-studied adiposity phenotypes also predict other adiposity measures in 2420 African American individuals from the Jackson Heart Study.MethodsPolygenic risk scores (PRS) for BMI, WHR adjusted for BMI (WHRBMIadj), WCBMIadj, and body fat percentage (BF%) were calculated using GWAS significant variants from mostly European ancestry studies. Associations between each PRS and adiposity measures were examined using multivariable linear regression.ResultsThe BMI-PRS was found to be a positive predictor of BF% (β=0.005 per allele, 95% CI: 0.002, 0.008) and subcutaneous adiposity (β=0.004, CI: 0.002, 0.008). The BF%-PRS was associated with subcutaneous (β=0.022, CI: 0.010, 0.032) but not visceral adiposity; neither BMI nor BF%-PRS were predictors of central obesity measures. Other PRS were not associated with BF%.ConclusionThese analyses suggest: (a) genetically driven increases in BF% strongly associate with subcutaneous but not visceral adiposity; (b) BF% is strongly associated with BMI but not central adiposity associated genetic variants. How these variants may contribute to observed differences in adiposity patterns between African and European ancestry individuals requires further study.

Abstract P227: Direct Association of Adiponectin with Individual European Ancestry in African Americans: the Jackson Heart Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Aurelian Bidulescu ◽  
Shweta Choudhry ◽  
Sarah G Buxbaum ◽  
Jiankang Liu ◽  
Dorothy L Coverson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
African Americans ◽  
Waist Circumference ◽  
European Ancestry ◽  
Jackson Heart Study ◽  
Community Based ◽  
Plasma Adiponectin ◽  
Heart Study ◽  
Direct Association ◽  
The Individual

Background: Compared with European Americans, African Americans exhibit lower levels of the cardio-metabolically protective adipokine known as adiponectin even after accounting for adiposity measures. Few studies have examined the association between adiponectin and individual ancestry estimates in African Americans, and most of these studies used only a few hundreds of the ancestry informative markers (AIMs). Therefore, we employed a relatively dense panel of AIMs to estimate the individual proportions of European ancestry (PEA) for the African Americans enrolled in a large community-based cohort in order to test the hypothesis that plasma adiponectin and PEA are directly associated. Methods: Plasma specimens from 1,439 participants with available DNA in the Jackson Heart Study were analyzed by ELISA for adiponectin levels. Using pseudo-ancestral population genotype data from the International HapMap Consortium, PEA was estimated for each individual with a panel of up to 1,447 genome-wide preselected AIMs by a maximum likelihood approach. Insulin resistance, defined as the highest quartile, was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR) and obesity by a body mass index (BMI) greater or equal to 30 kg/m 2 . Interaction assessment and stepwise linear regression models were used to analyze the cross-sectional association between adiponectin and PEA. A p-value less than 0.05 was considered significant for the main and the interactive effects. Results: Among the study participants (62% women; mean age 48 ± 12 years), the median (interquartile range) of PEA was 15.8 (9.3)%. BMI ( p = .0004 ) and insulin resistance ( p = .002 ) were effect modifiers of the assessed association, but not sex ( p = .31 ) or waist circumference ( p = .62 ). Among non-obese individuals (n = 673), adiponectin was directly associated with PEA (β = 3.3 ± 1.5, p = .03 ) after adjustment for age, sex, waist circumference, systolic blood pressure, HOMA-IR, cholesterol fractions, C-reactive protein, physical activity and, in the initial stepwise models, measures of socioeconomic status. Among participants without insulin resistance (n = 1,141), after adjustment for the same variables with the exception of age and HOMA-IR (as indicated by the stepwise procedure), a direct association between adiponectin and PEA was also observed (β = 4.4 ± 1.3, p = .0005 ). Conclusions: In a large community-based African American population, the individual proportion of the global European ancestry was directly associated with plasma adiponectin among participants without impaired lipid or glucose metabolism, namely among those without obesity or insulin-resistance. Our study results point to the genetic origins of the lower levels of adiponectin in African Americans and warrant further exploration of the role ancestry plays in the complex relationship of adiponectin with cardio-metabolic risk factors.

Abstract 2924: Association of NOS1AP Genetic Variants with QT Interval Duration in Families from the Diabetes Heart Study

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Allison B Lehtinen ◽  
Christopher Newton-Cheh ◽  
Julie T Ziegler ◽  
Carl D Langefeld ◽  
Barry I Freedman ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Qt Interval ◽  
Genetic Model ◽  
Additive Model ◽  
Adaptor Protein ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Interval Duration ◽  
Common Genetic Variants ◽  
Qt Interval Duration

Background: Prolongation of the electrocardiographic QT interval is a risk factor for sudden cardiac death (SCD) in unselected samples as well as in post-myocardial infarction patients or those with diabetes. Common genetic variants in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene have been reported to be associated with QT interval duration in individuals of European ancestry. We sought to replicate the association of NOS1AP variants with QT interval duration in pedigrees enriched for type 2 diabetes mellitus (T2DM). Methods and Results: Two single nucleotide polymorphisms (SNPs) in the NOS1AP gene, rs10494366 and rs10918594, were genotyped in a collection of 937 European Americans (EAs) and 177 African Americans (AAs) in 450 pedigrees containing at least two siblings with T2DM. An additive genetic model was tested for each SNP in ancestry-specific analyses using SOLAR in the total sample and in the diabetic subset (EA n=778, AA n=159), with and without exclusion of QT-altering medications. In the EA individuals, rs10494366 minor allele homozygotes had an 8.9 msec longer mean QT interval compared to major homozygotes (additive model p=4.4x10 -3 ); rs10918594 minor homozygotes had a 12.9 msec longer mean QT interval compared to major homozygotes (p=9.9x10 -5 ). Excluding users of QT-altering medications in the diabetic-only EA sample (n=514) strengthened the association despite the reduction in sample size (20.6 msec difference, p=2.0x10 -5 ; 23.4 msec difference, p=8.9x10 -7 , respectively). No association between the NOS1AP SNPs and QT interval duration was observed in the limited number of AA individuals examined. Conclusions: Two NOS1AP SNPs are strongly associated with QT interval duration in a predominately diabetic EA sample. Stronger effects of NOS1AP variants in diabetic individuals compared to previously reported unselected samples suggest that this patient subset may be particularly susceptible to genetic variants that influence myocardial depolarization and repolarization as manifest in the QT interval.

Abstract MP56: A Gene-centric Association Study of Activated Partial Thromoplastin Time in European Americans and African Americans: The ARIC Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Lu-Chen Weng ◽  
Weihong Tang ◽  
Mary Cushman ◽  
James S Pankow ◽  
Saonli Basu ◽  
...  
Keyword(s):  
African Americans ◽  
Candidate Gene ◽  
Genetic Variants ◽  
European Ancestry ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Link Type ◽  
European Americans ◽  
Common Genetic Variants ◽  
Aric Study

Introduction: Activated partial thromboplastin time (aPTT) is commonly used to screen for coagulation factor deficiencies. Shorter aPTT is also a risk marker for incident and recurrent venous thromboembolism (VTE). Genetic factors influencing aPTT are not well understood. aPTT was associated with common genetic variants of coagulation factors V (F5), XI (F11), XII (F12), KNG1, HRG, and ABO in previously reported genome-wide association studies (GWAS) that were conducted in individuals of European ancestry; no data have been reported in other race groups. Hypothesis: The present study aimed to identify aPTT-related gene variants in European Americans (EAs) and African Americans (AAs). Methods: We conducted a large-scale candidate gene study for aPTT in 9,719 EAs and 2,799 AAs from the Atherosclerosis Risk in Communities (ARIC) study. Subjects on anticoagulants were excluded. Nearly 50,000 single nucleotide polymorphisms (SNPs) located in 2,100 candidate genes were genotyped by the Candidate gene Association Resource (CARe) gene chip. The association between each SNP and aPTT was assessed with an additive genetic model using linear regression adjusted for age, sex, and field center. We additionally adjusted for principal components in AAs to account for potential population stratification. P-value for significant threshold was set at 2x10-6 after accounting for multiple testing. Results: In EAs, fifty-five SNPs from F5, HRG, KNG1, F11, F12, and ABO genes exceeded the significant p-value threshold. The signals in HRG, KNG1, F11, F12, and ABO genes replicated the previously reported GWAS findings. The top variant in F5 identified in EAs was only weakly associated with the previously reported GWAS variant (rs2239852, p=1.89x10-08 and r2=0.02 with rs9332701 reported in the previously reported GWAS). In AAs, twenty-seven SNPs from the HRG, KNG1, F12, and ABO genes were significantly associated with aPTT. The top signals from the HRG (rs9898, p=1.19x10-27) and KNG1 genes ( rs710446 , p=8.41x10-42) replicated the previously reported signals in EAs with similar effect size and direction of association, but the top signals in the F12 and ABO genes were weakly associated with the previously reported variants in EAs (rs1801020 in F12: p=1.01x10-84 and r2=0.12 with rs2545801, and rs8176722 in ABO: p=1.62x10-29 and r2=0.26 with rs687621 , respectively). Conclusions: Our study replicated the previously reported associations of aPTT with HRG, KNG1, F11, F12, and ABO genes in EAs and with HRG and KNG1 in AAs. The signals from F5 identified in EAs and from F12 and ABO identified in AAs may represent new genetic variants for aPTT.

Abstract 4401: Two Independent Genetic Variants in NOS1AP are Associated with QT interval in a Multi-Ethnic Population: the Dallas Heart Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dan E Arking ◽  
Amit Khera ◽  
Chao Xing ◽  
Wen H Kao ◽  
Aravinda Chakravarti
Keyword(s):  
Heart Rate ◽  
Genetic Variants ◽  
Qt Interval ◽  
Genetic Model ◽  
Black Population ◽  
European Ancestry ◽  
Ethnic Population ◽  
Heart Study ◽  
Increased Risk ◽  
Dallas Heart Study

Extremes of QT interval are associated with increased risk for sudden cardiac death (SCD), and thus identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous work revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We thus sought to characterize the effects of NOS1AP genetic variants in the multi-ethnic population-based Dallas Heart Study (DHS). Among 3,557 participants in DHS with available DNA, those without QT interval, heart rate, age, and/or sex information, and those with QRS >120 or undetermined ethnicity were excluded, resulting in 2,949 samples available for analysis (501 Hispanic, 1,506 Black, 942 White). Sex- and ethnicity-stratified linear regression was used to correct QT interval for heart rate and age. Eight SNPs spanning the region previously associated with QT interval were genotyped, and ethnic-specific analyses were performed under an additive genetic model. The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in the White participants (+2.6 ms, P<0.005) as well as in Blacks (+3.2 ms, P<3.6 × 10 –5), with the same direction of effect in Hispanics (+1.5 ms, P<0.17). A second SNP, rs16856785, which was uncorrelated with rs16847548 (r2 < 0.01 in Blacks) was also associated with QT interval in Blacks (+1.6 ms, P<0.01), with qualitatively similar results in Whites (+0.9 ms, P<0.33) and Hispanics (+0.6 ms, P<0.66). Adjusting for local and global ancestry using Ancestry Informative Markers did not significantly alter the results. Comparing Blacks homozygous at both SNPs for the QT lengthening allele to Blacks homozygous for the complementary alleles revealed a 13.9 ms difference in QT interval. These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends in Hispanics. Further, a second, independent site within NOS1AP has been implicated in modulating QT interval, highlighting the importance of NOS1AP genetic variants in regulating QT interval.

scholarly journals Contributions of common genetic variants to risk of schizophrenia among individuals of African and Latino ancestry

2019 ◽  
Vol 25 (10) ◽  
pp. 2455-2467 ◽  
Author(s):  
Tim B. Bigdeli ◽  
◽  
Giulio Genovese ◽  
Penelope Georgakopoulos ◽  
Jacquelyn L. Meyers ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Association Studies ◽  
Large Fraction ◽  
African Ancestry ◽  
Common Variant ◽  
Human Populations ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
Common Genetic Variants

Abstract Schizophrenia is a common, chronic and debilitating neuropsychiatric syndrome affecting tens of millions of individuals worldwide. While rare genetic variants play a role in the etiology of schizophrenia, most of the currently explained liability is within common variation, suggesting that variation predating the human diaspora out of Africa harbors a large fraction of the common variant attributable heritability. However, common variant association studies in schizophrenia have concentrated mainly on cohorts of European descent. We describe genome-wide association studies of 6152 cases and 3918 controls of admixed African ancestry, and of 1234 cases and 3090 controls of Latino ancestry, representing the largest such study in these populations to date. Combining results from the samples with African ancestry with summary statistics from the Psychiatric Genomics Consortium (PGC) study of schizophrenia yielded seven newly genome-wide significant loci, and we identified an additional eight loci by incorporating the results from samples with Latino ancestry. Leveraging population differences in patterns of linkage disequilibrium, we achieve improved fine-mapping resolution at 22 previously reported and 4 newly significant loci. Polygenic risk score profiling revealed improved prediction based on trans-ancestry meta-analysis results for admixed African (Nagelkerke’s R2 = 0.032; liability R2 = 0.017; P < 10−52), Latino (Nagelkerke’s R2 = 0.089; liability R2 = 0.021; P < 10−58), and European individuals (Nagelkerke’s R2 = 0.089; liability R2 = 0.037; P < 10−113), further highlighting the advantages of incorporating data from diverse human populations.

Performance of polygenic risk scores for cancer prediction in an academic biobank.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1528-1528
Author(s):  
Heena Desai ◽  
Anh Le ◽  
Ryan Hausler ◽  
Shefali Verma ◽  
Anurag Verma ◽  
...  
Keyword(s):  
Risk Score ◽  
Genetic Variants ◽  
Association Studies ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
European Americans ◽  
Genome Wide ◽  
Common Genetic Variants

1528 Background: The discovery of rare genetic variants associated with cancer have a tremendous impact on reducing cancer morbidity and mortality when identified; however, rare variants are found in less than 5% of cancer patients. Genome wide association studies (GWAS) have identified hundreds of common genetic variants significantly associated with a number of cancers, but the clinical utility of individual variants or a polygenic risk score (PRS) derived from multiple variants is still unclear. Methods: We tested the ability of polygenic risk score (PRS) models developed from genome-wide significant variants to differentiate cases versus controls in the Penn Medicine Biobank. Cases for 15 different cancers and cancer-free controls were identified using electronic health record billing codes for 11,524 European American and 5,994 African American individuals from the Penn Medicine Biobank. Results: The discriminatory ability of the 15 PRS models to distinguish their respective cancer cases versus controls ranged from 0.68-0.79 in European Americans and 0.74-0.93 in African Americans. Seven of the 15 cancer PRS trended towards an association with their cancer at a p<0.05 (Table), and PRS for prostate, thyroid and melanoma were significantly associated with their cancers at a bonferroni corrected p<0.003 with OR 1.3-1.6 in European Americans. Conclusions: Our data demonstrate that common variants with significant associations from GWAS studies can distinguish cancer cases versus controls for some cancers in an unselected biobank population. Given the small effects, future studies are needed to determine how best to incorporate PRS with other risk factors in the precision prediction of cancer risk. [Table: see text]

scholarly journals Associations of adiponectin with individual European ancestry in African Americans: the Jackson Heart Study

2014 ◽  
Vol 5 ◽  
Author(s):  
Aurelian Bidulescu ◽  
Shweta Choudhry ◽  
Solomon K. Musani ◽  
Sarah G. Buxbaum ◽  
Jiankang Liu ◽  
...  
Keyword(s):  
African Americans ◽  
European Ancestry ◽  
Jackson Heart Study ◽  
Heart Study

scholarly journals Integration of rare large-effect expression variants improves polygenic risk prediction

2020 ◽  
Author(s):  
Craig Smail ◽  
Nicole M. Ferraro ◽  
Matthew G. Durrant ◽  
Abhiram S. Rao ◽  
Matthew Aguirre ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Rare Variants ◽  
Complex Trait ◽  
Risk Scores ◽  
Multiple Traits ◽  
Polygenic Risk ◽  
Common Genetic Variants ◽  
Using Data ◽  
The Uk ◽  
The Impact

SummaryPolygenic risk scores (PRS) aim to quantify the contribution of multiple genetic loci to an individual’s likelihood of a complex trait or disease. However, existing PRS estimate genetic liability using common genetic variants, excluding the impact of rare variants. We identified rare, large-effect variants in individuals with outlier gene expression from the GTEx project and then assessed their impact on PRS predictions in the UK Biobank (UKB). We observed large deviations from the PRS-predicted phenotypes for carriers of multiple outlier rare variants; for example, individuals classified as “low-risk” but in the top 1% of outlier rare variant burden had a 6-fold higher rate of severe obesity. We replicated these findings using data from the NHLBI Trans-Omics for Precision Medicine (TOPMed) biobank and the Million Veteran Program, and demonstrated that PRS across multiple traits will significantly benefit from the inclusion of rare genetic variants.

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