BACKGROUND: We conducted admixture mapping and fine-mapping analyses to identify ancestry-of-origin loci influencing cognitive abilities.
METHODS: We estimated the association of local ancestry intervals across the genome with five neurocognitive measures in 7140 diverse Hispanic and Latino adults (mean age 55 years). We prioritized genetic variants in associated loci and tested them for replication in four independent cohorts.
RESULTS: We identified nine local ancestry-associated regions for the five neurocognitive measures. There was strong biological support for the observed associations to cognitive function at all loci and there was statistical evidence of independent replication at 4q12, 9p22.1, and 13q12.13.
CONCLUSIONS: Our study identified multiple novel loci harboring genes implicated in cognitive functioning and dementia, and uncovered ancestry-relevant genetic variants. It adds to our understanding of the genetic architecture of cognitive function in Hispanic and Latino adults and demonstrates the power of admixture mapping to discover unique haplotypes influencing cognitive function, complementing genome-wide association studies.
CONCLUSIONS: We identified nine ancestry-of-origin chromosomal regions associated with five neurocognitive traits. In each associated region, we identified single nucleotide polymorphisms (SNPs) that explained, at least in part, the admixture signal and were tested for replication in independent samples of Black, non-Hispanic White, and Hispanic/Latino adults with the same or similar neurocognitive tests. Statistical evidence of independent replication of the prioritized SNPs was observed for three of the nine associations, at chr4q12, chr9p22.1, and chr13q12.13. At all loci, there was strong biological support for the observed associations to cognitive function and dementia, prioritizing genes such as KIT, implicated in autophagic clearance of neurotoxic proteins and on mast cell and microglial-mediated inflammation; SLC24A2, implicated in synaptic plasticity associated with learning and memory; and MTMR6, implicated in phosphoinositide lipids metabolism.

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). We conducted a trans-ancestral GWAS with summary statistics from HISLA stage 1 and existing consortia of European and African ancestries. In our HISLA stage 1 + 2 analyses, we discovered one BMI locus, as well as two BMI signals and another height signal each within established anthropometric loci. In our trans-ancestral meta-analysis, we discovered three BMI loci, one height locus, and one WHRadjBMI locus. We also identified 3 secondary signals for BMI, 28 for height, and 2 for WHRadjBMI in established loci. We show that 336 known BMI, 1,177 known height, and 143 known WHRadjBMI (combined) SNPs demonstrated suggestive transferability (nominal significance and effect estimate directional consistency) in Hispanic/Latino adults. Of these, 36 BMI, 124 height, and 11 WHRadjBMI SNPs were significant after trait-specific Bonferroni correction. Trans-ancestral meta-analysis of the three ancestries showed a small-to-moderate impact of uncorrected population stratification on the resulting effect size estimates. Our findings demonstrate that future studies may also benefit from leveraging diverse ancestries and differences in linkage disequilibrium patterns to discover novel loci and additional signals with less residual population stratification.

BACKGROUND: Cardiovascular disease (CVD) risk factor control is a cornerstone of diabetes mellitus management. Little is known about relationships of objectively measured sedentary time and physical activity with major CVD risk factor control in individuals with diabetes mellitus. We examined associations of objectively measured sedentary time and moderate-to-vigorous physical activity with reaching major CVD risk factor control goals among US Hispanic/Latino adults with diabetes mellitus.
RESULTS: This cross-sectional analysis included 1699 participants with diabetes mellitus from the Hispanic Community Health Study/Study of Latinos (2008-2011). Logistic regression models were used to estimate the odds ratios (ORs) of meeting the following 5 major CVD risk factor control goals: hemoglobin A1c <7.0%; systolic/diastolic blood pressure <140/80 mm Hg; triglycerides <150 mg/dL; low-density lipoprotein cholesterol <100 mg/dL; and high-density lipoprotein cholesterol >40/50 mg/dL for men/women. After adjustment for covariates including moderate-to-vigorous physical activity, less sedentary time was associated with increased odds of reaching hemoglobin A1c (OR=1.76 [95% CI: 1.10, 2.82]) and triglyceride control goals (OR=2.16 [1.36, 3.46]), and reaching ≥3 CVD risk factor control goals (OR=2.08 [1.34, 3.23]) (all ORs for comparisons of extreme tertiles of sedentary time). Moderate-to-vigorous physical activity was not associated with reaching any CVD risk factor control goals. Substituting 60-min/day of sedentary time with light-intensity physical activity was associated with increased odds of reaching hemoglobin A1c (OR=1.18 [1.04, 1.35]), high-density lipoprotein cholesterol (OR=1.17 [1.04, 1.32]), and triglyceride (OR=1.20 [1.05, 1.36]) control goals.
CONCLUSIONS: Among US Hispanic/Latino adults with diabetes mellitus, less sedentary time, but not moderate-to-vigorous physical activity, was associated with improved CVD risk factor control, specifically in reaching hemoglobin A1c and triglyceride control goals.