Table2_Evaluation of 71 Coronary Artery Disease Risk Variants in a Multiethnic Cohort.xlsx

Background<p>Coronary heart disease (CHD) is the most common cause of death worldwide. Previous studies have identified numerous common CHD susceptibility loci, with the vast majority identified in populations of European ancestry. How well these findings transfer to other racial/ethnic populations remains unclear.</p>Methods and Results<p>We examined the generalizability of the associations with 71 known CHD loci in African American, Latino and Japanese men and women in the Multiethnic Cohort (6,035 cases and 11,251 controls). In the combined multiethnic sample, 78% of the loci demonstrated odds ratios that were directionally consistent with those previously reported (p = 2 × 10⁻⁶), with this fraction ranging from 59% in Japanese to 70% in Latinos. The number of nominally significant associations across all susceptibility regions ranged from only 1 in Japanese to 11 in African Americans with the most statistically significant association observed through locus fine-mapping noted for rs3832016 (OR = 1.16, p = 2.5×10⁻⁵) in the SORT1 region on chromosome 1p13. Lastly, we examined the cumulative predictive effect of CHD SNPs across populations with improved power by creating genetic risk scores (GRSs) that summarize an individual’s aggregated exposure to risk variants. We found the GRSs to be significantly associated with risk in African Americans (OR = 1.03 per allele; p = 4.1×10⁻⁵) and Latinos (OR = 1.03; p = 2.2 × 10⁻⁸), but not in Japanese (OR = 1.01; p = 0.11).</p>Conclusions<p>While a sizable fraction of the known CHD loci appear to generalize in these populations, larger fine-mapping studies will be needed to localize the functional alleles and better define their contribution to CHD risk in these populations.</p

Table4_Evaluation of 71 Coronary Artery Disease Risk Variants in a Multiethnic Cohort.xlsx

Background<p>Coronary heart disease (CHD) is the most common cause of death worldwide. Previous studies have identified numerous common CHD susceptibility loci, with the vast majority identified in populations of European ancestry. How well these findings transfer to other racial/ethnic populations remains unclear.</p>Methods and Results<p>We examined the generalizability of the associations with 71 known CHD loci in African American, Latino and Japanese men and women in the Multiethnic Cohort (6,035 cases and 11,251 controls). In the combined multiethnic sample, 78% of the loci demonstrated odds ratios that were directionally consistent with those previously reported (p = 2 × 10⁻⁶), with this fraction ranging from 59% in Japanese to 70% in Latinos. The number of nominally significant associations across all susceptibility regions ranged from only 1 in Japanese to 11 in African Americans with the most statistically significant association observed through locus fine-mapping noted for rs3832016 (OR = 1.16, p = 2.5×10⁻⁵) in the SORT1 region on chromosome 1p13. Lastly, we examined the cumulative predictive effect of CHD SNPs across populations with improved power by creating genetic risk scores (GRSs) that summarize an individual’s aggregated exposure to risk variants. We found the GRSs to be significantly associated with risk in African Americans (OR = 1.03 per allele; p = 4.1×10⁻⁵) and Latinos (OR = 1.03; p = 2.2 × 10⁻⁸), but not in Japanese (OR = 1.01; p = 0.11).</p>Conclusions<p>While a sizable fraction of the known CHD loci appear to generalize in these populations, larger fine-mapping studies will be needed to localize the functional alleles and better define their contribution to CHD risk in these populations.</p

Image2_Evaluation of 71 Coronary Artery Disease Risk Variants in a Multiethnic Cohort.pdf

Background<p>Coronary heart disease (CHD) is the most common cause of death worldwide. Previous studies have identified numerous common CHD susceptibility loci, with the vast majority identified in populations of European ancestry. How well these findings transfer to other racial/ethnic populations remains unclear.</p>Methods and Results<p>We examined the generalizability of the associations with 71 known CHD loci in African American, Latino and Japanese men and women in the Multiethnic Cohort (6,035 cases and 11,251 controls). In the combined multiethnic sample, 78% of the loci demonstrated odds ratios that were directionally consistent with those previously reported (p = 2 × 10⁻⁶), with this fraction ranging from 59% in Japanese to 70% in Latinos. The number of nominally significant associations across all susceptibility regions ranged from only 1 in Japanese to 11 in African Americans with the most statistically significant association observed through locus fine-mapping noted for rs3832016 (OR = 1.16, p = 2.5×10⁻⁵) in the SORT1 region on chromosome 1p13. Lastly, we examined the cumulative predictive effect of CHD SNPs across populations with improved power by creating genetic risk scores (GRSs) that summarize an individual’s aggregated exposure to risk variants. We found the GRSs to be significantly associated with risk in African Americans (OR = 1.03 per allele; p = 4.1×10⁻⁵) and Latinos (OR = 1.03; p = 2.2 × 10⁻⁸), but not in Japanese (OR = 1.01; p = 0.11).</p>Conclusions<p>While a sizable fraction of the known CHD loci appear to generalize in these populations, larger fine-mapping studies will be needed to localize the functional alleles and better define their contribution to CHD risk in these populations.</p

Table5_Evaluation of 71 Coronary Artery Disease Risk Variants in a Multiethnic Cohort.xlsx

Background<p>Coronary heart disease (CHD) is the most common cause of death worldwide. Previous studies have identified numerous common CHD susceptibility loci, with the vast majority identified in populations of European ancestry. How well these findings transfer to other racial/ethnic populations remains unclear.</p>Methods and Results<p>We examined the generalizability of the associations with 71 known CHD loci in African American, Latino and Japanese men and women in the Multiethnic Cohort (6,035 cases and 11,251 controls). In the combined multiethnic sample, 78% of the loci demonstrated odds ratios that were directionally consistent with those previously reported (p = 2 × 10⁻⁶), with this fraction ranging from 59% in Japanese to 70% in Latinos. The number of nominally significant associations across all susceptibility regions ranged from only 1 in Japanese to 11 in African Americans with the most statistically significant association observed through locus fine-mapping noted for rs3832016 (OR = 1.16, p = 2.5×10⁻⁵) in the SORT1 region on chromosome 1p13. Lastly, we examined the cumulative predictive effect of CHD SNPs across populations with improved power by creating genetic risk scores (GRSs) that summarize an individual’s aggregated exposure to risk variants. We found the GRSs to be significantly associated with risk in African Americans (OR = 1.03 per allele; p = 4.1×10⁻⁵) and Latinos (OR = 1.03; p = 2.2 × 10⁻⁸), but not in Japanese (OR = 1.01; p = 0.11).</p>Conclusions<p>While a sizable fraction of the known CHD loci appear to generalize in these populations, larger fine-mapping studies will be needed to localize the functional alleles and better define their contribution to CHD risk in these populations.</p

Table3_Evaluation of 71 Coronary Artery Disease Risk Variants in a Multiethnic Cohort.xlsx

Background<p>Coronary heart disease (CHD) is the most common cause of death worldwide. Previous studies have identified numerous common CHD susceptibility loci, with the vast majority identified in populations of European ancestry. How well these findings transfer to other racial/ethnic populations remains unclear.</p>Methods and Results<p>We examined the generalizability of the associations with 71 known CHD loci in African American, Latino and Japanese men and women in the Multiethnic Cohort (6,035 cases and 11,251 controls). In the combined multiethnic sample, 78% of the loci demonstrated odds ratios that were directionally consistent with those previously reported (p = 2 × 10⁻⁶), with this fraction ranging from 59% in Japanese to 70% in Latinos. The number of nominally significant associations across all susceptibility regions ranged from only 1 in Japanese to 11 in African Americans with the most statistically significant association observed through locus fine-mapping noted for rs3832016 (OR = 1.16, p = 2.5×10⁻⁵) in the SORT1 region on chromosome 1p13. Lastly, we examined the cumulative predictive effect of CHD SNPs across populations with improved power by creating genetic risk scores (GRSs) that summarize an individual’s aggregated exposure to risk variants. We found the GRSs to be significantly associated with risk in African Americans (OR = 1.03 per allele; p = 4.1×10⁻⁵) and Latinos (OR = 1.03; p = 2.2 × 10⁻⁸), but not in Japanese (OR = 1.01; p = 0.11).</p>Conclusions<p>While a sizable fraction of the known CHD loci appear to generalize in these populations, larger fine-mapping studies will be needed to localize the functional alleles and better define their contribution to CHD risk in these populations.</p

Table7_Evaluation of 71 Coronary Artery Disease Risk Variants in a Multiethnic Cohort.xlsx

Background<p>Coronary heart disease (CHD) is the most common cause of death worldwide. Previous studies have identified numerous common CHD susceptibility loci, with the vast majority identified in populations of European ancestry. How well these findings transfer to other racial/ethnic populations remains unclear.</p>Methods and Results<p>We examined the generalizability of the associations with 71 known CHD loci in African American, Latino and Japanese men and women in the Multiethnic Cohort (6,035 cases and 11,251 controls). In the combined multiethnic sample, 78% of the loci demonstrated odds ratios that were directionally consistent with those previously reported (p = 2 × 10⁻⁶), with this fraction ranging from 59% in Japanese to 70% in Latinos. The number of nominally significant associations across all susceptibility regions ranged from only 1 in Japanese to 11 in African Americans with the most statistically significant association observed through locus fine-mapping noted for rs3832016 (OR = 1.16, p = 2.5×10⁻⁵) in the SORT1 region on chromosome 1p13. Lastly, we examined the cumulative predictive effect of CHD SNPs across populations with improved power by creating genetic risk scores (GRSs) that summarize an individual’s aggregated exposure to risk variants. We found the GRSs to be significantly associated with risk in African Americans (OR = 1.03 per allele; p = 4.1×10⁻⁵) and Latinos (OR = 1.03; p = 2.2 × 10⁻⁸), but not in Japanese (OR = 1.01; p = 0.11).</p>Conclusions<p>While a sizable fraction of the known CHD loci appear to generalize in these populations, larger fine-mapping studies will be needed to localize the functional alleles and better define their contribution to CHD risk in these populations.</p

Selected Population Characteristics by Genome-Wide Association Study Stage and Case-Control Status Among Women of European Ancestry.

<p>Abbreviations: BMI, body mass index; GRS, genetic risk score; GWAS, genome-wide association study; N, sample size; SD standard deviation.</p><p>Selected Population Characteristics by Genome-Wide Association Study Stage and Case-Control Status Among Women of European Ancestry.</p

Endometrial Cancer Risk within BMI and BMI GRS Subgroups.

<p>Data represent odds ratios and 95% confidence intervals of endometrial cancer for quartile 1 (Q1; 67.5–87.1 risk alleles), the interquartile range (IQR; 87.2–95.5 risk alleles), and quartile 4 (Q4; 95.6–115.3 risk alleles) categories of the BMI GRS among normal weight (<25 kg/m²), overweight (25–29.9 kg/m²), and obese (30+ kg/m²) women.</p

Genetic Risk Scores Based on Biologic Single Nucleotide Polymorphism Subsets and Endometrial Cancer Risk Among Women of European Ancestry.

<p>Abbreviations: BMI, body mass index; CI, confidence interval; OR, odds ratio.</p><p>^a Unconditional logistic regression models adjusted for age at diagnosis and study were used to estimate per risk allele odds ratios and 95% confidence intervals</p><p>^b Unconditional logistic regression models were additionally adjusted for BMI</p><p>Genetic Risk Scores Based on Biologic Single Nucleotide Polymorphism Subsets and Endometrial Cancer Risk Among Women of European Ancestry.</p

Body Mass Index Genetic Risk Score and Endometrial Cancer Risk Among Women of European Ancestry.

<p>Abbreviations: BMI, body mass index; CI, confidence interval; OR, odds ratio.</p><p>^a Unconditional logistic regression models adjusted for age at diagnosis and study were used to estimate odds ratios and 95% confidence intervals</p><p>^b Unconditional logistic regression models were additionally adjusted for BMI</p><p>^c Per 10 BMI risk alleles</p><p>Body Mass Index Genetic Risk Score and Endometrial Cancer Risk Among Women of European Ancestry.</p