The apoE4 isoform is associated with increased cholesterol, cardiovascular risk, and Alzheimer's Disease risk, however, its distribution is not well-understood among US Latinos. Latinos living in the US are highly Amerindian, European and African admixed, which varies by region and country of origin. However, Latino genetic diversity is understudied and consequently poorly understood, which has significant implications for understanding disease risk in nearly one-fifth of the US population. In this report we describe apoE distributions in a large and representative sample of diverse, genetically determined US Latinos.

Background

Studies found associations between pulmonary function (PF) and cognition, but these are limited by mostly cross-sectional design and a single measure of PF (typically forced expiratory volume in 1 second [FEV1]). Our objective was to prospectively analyze the association of repeatedly measured PF with cognition.

Methods

We studied 3 499 participants in the Coronary Artery Risk Development in Young Adults cohort with cognition measured at year 25 (Y25) and Y30, and PF (FEV1 and forced vital capacity [FVC], reflecting better PF) measured up to 6 times from Y0 to Y20. Cognition was measured via Stroop test, Rey-Auditory Verbal Learning Test [RAVLT], and digit symbol substitution test [DSST], which capture executive function, verbal learning and memory, and attention and psychomotor speed, respectively; lower Stroop, and higher RAVLT and DSST scores indicate better cognition. We modeled linear, cross-sectional associations between cognition and PF at Y30 (mean age 55), and mixed models to examine associations between cognition at Y25-Y30 and longitudinal PF (both annual rate of change, and cumulative PF from Y0 to Y20).

Results

At Y30, FEV1 and FVC were cross-sectionally associated with all 3 measures of cognition (β = 0.08-0.12, p < .01-.02). Annual change from peak FEV1/FVC ratio was associated with Stroop and DSST (β = 18.06, 95% CI = 7.71-28.40; β = 10.30, 95% CI = 0.26-20.34, respectively), but not RAVLT. Cumulative FEV1 and FVC were associated with Stroop and DSST (β = 0.07-0.12, p < .01-.02), but only cumulative FEV1 was associated with RAVLT (β = 0.07, 95% CI = 0.00-0.14).

Conclusions

We identified prospective associations between measures of PF and cognition even at middle ages, adding evidence of a prospective association between reduced PF and cognitive decline.

In a large cohort of 1,772 participants from the Hispanic Community Health Study/Study of Latinos with overlapping 16SV4 rRNA gene (bacterial amplicon), ITS1 (fungal amplicon), and shotgun sequencing data, we demonstrate that 16SV4 amplicon sequencing and shotgun metagenomics offer the same level of taxonomic accuracy for bacteria at the genus level even at shallow sequencing depths. In contrast, for fungal taxa, we did not observe meaningful agreements between shotgun and ITS1 amplicon results. Finally, we show that amplicon and shotgun data can be harmonized and pooled to yield larger microbiome datasets with excellent agreement (<1% effect size variance across three independent outcomes) using pooled amplicon/shotgun data compared to pure shotgun metagenomic analysis. Thus, there are multiple approaches to study the microbiome in epidemiological studies, and we provide a demonstration of a powerful pooling approach that will allow researchers to leverage the massive amount of amplicon sequencing data generated over the last two decades.

BACKGROUND: Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study. METHODS: 2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r(2)>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ± 100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis. RESULTS: Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p<0.05) for 15 SNPs, while 32 more were directionally consistent with previous reports. Risk score was a significant predictor with a 2.03 fold higher risk CI (1.69-2.44) of T2D comparing the highest to lowest quintile of risk allele burden (p = 5.72 × 10(-14)). Two improved SNPs around index rs10923931 and 5 new candidate SNPs around indices rs10965250 and rs1111875 passed simple Bonferroni corrections for significance in conditional analysis. Nonetheless, only a small fraction (2.3% on the disease liability scale) of T2D burden in Singapore is explained by these SNPs. CONCLUSIONS: While diabetes risk in Singapore Chinese involves genetic variants, most disease risk remains unexplained. Further genetic work is ongoing in the Singapore Chinese population to identify unique common variants not already seen in earlier studies. However rapid increases in T2D risk have occurred in recent decades in this population, indicating that dynamic environmental influences and possibly gene by environment interactions complicate the genetic architecture of this disease.

Objective

The purpose of this study is to examine the association between verbal learning, fluency, and processing speed with anxious depression symptomatology (ADS) among diverse Hispanics. We hypothesized an inverse association of anxious depression with neurocognition among Hispanics of different heritage.

Design

Data are from the Hispanic Community Health Study/Study of Latinos. The sample included 9,311participants aged 45-74 years (mean: 56.5 years). A latent class analysis of items from the Center for Epidemiological Studies for Depression scale and the Spielberger Trait Anxiety Inventory was used to derive an anxious depression construct. Neurocognitive measures included scores on the Brief Spanish English Verbal Learning Test (B-SEVLT, learning and recall trials), Word Fluency (WF), Digit Symbol Substitution (DSS) test, and a Global Cognitive Score (GCS). We fit survey linear regression models to test the associations between anxious depression symptomatology and cognitive function. We tested for effect modification by sex, Hispanic heritage, and age groups.

Results

Among men, 71.6% reported low, 23.3% moderate, and 5.1% high ADS. Among women, 55.1% reported low, 33.2% moderate, and 11.8% high ADS. After controlling for age, sex, sociodemographic characteristics, cardiovascular risk factors and disease, and antidepressant use, we found significant inverse associations between moderate and high anxious depression (ref:low) with B-SEVLT learning and recall, DSS and GCS. Moderate, but not high, anxious depression was inversely associated with WF. Associations were not modified by sex, Hispanic heritage, or age.

Conclusions

Increased anxious depression symptomatology is associated with decreased neurocognitive function among Hispanics. Longitudinal studies are needed to establish temporality and infer if negative emotional symptoms precede cognitive deficits.

Introduction

Reproductive health history may contribute to cognitive aging and risk for Alzheimer's disease, but this is understudied among Hispanic/Latina women.

Methods

Participants included 2126 Hispanic/Latina postmenopausal women (44 to 75 years) from the Study of Latinos-Investigation of Neurocognitive Aging. Survey linear regressions separately modeled the associations between reproductive health measures (age at menarche, history of oral contraceptive use, number of pregnancies, number of live births, age at menopause, female hormone use at Visit 1, and reproductive span) with cognitive outcomes at Visit 2 (performance, 7-year change, and mild cognitive impairment [MCI] prevalence).

Results

Younger age at menarche, oral contraceptive use, lower pregnancies, lower live births, and older age at menopause were associated with better cognitive performance. Older age at menarche was protective against cognitive change. Hormone use was linked to lower MCI prevalence.

Discussion

Several aspects of reproductive health appear to impact cognitive aging among Hispanic/Latina women.

Introduction

Apolipoprotein E (APOE) alleles are associated with cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease in Whites, but have weaker and inconsistent effects reported in Latinos. We hypothesized that this heterogeneity is due to ancestry-specific genetic effects.

Methods

We investigated the associations of the APOE alleles with significant cognitive decline and MCI in 4183 Latinos, stratified by six Latino backgrounds, and explored whether the proportion of continental genetic ancestry (European, African, and Amerindian) modifies these associations.

Results

APOE ε4 was associated with an increased risk of significant cognitive decline (odds ratio [OR] = 1.15, P-value = 0.03), with the strongest association in Cubans (OR = 1.46, P-value = 0.007). APOE-ε2 was associated with decreased risk of MCI (OR = 0.37, P-value = 0.04) in Puerto Ricans. Amerindian genetic ancestry was found to protect from the risk conferred by APOE ε4 on significant cognitive decline.

Discussion

Results suggest that APOE alleles' effects on cognitive outcomes differ across six Latino backgrounds and are modified by continental genetic ancestry.

BACKGROUND: Dietary patterns high in healthy minimally processed plant foods play an important role in modulating the gut microbiome and promoting cardiometabolic health. Little is known on the diet-gut microbiome relationship in US Hispanics/Latinos, who have a high burden of obesity and diabetes. OBJECTIVE: In a cross-sectional analysis, we sought to examine the relationships of 3 healthy dietary patterns-the alternate Mediterranean diet (aMED), the Healthy Eating Index (HEI)-2015, and the healthful plant-based diet index (hPDI)-with the gut microbiome in US Hispanic/Latino adults, and to study the association of diet-related species with cardiometabolic traits. METHODS: The Hispanic Community Health Study/Study of Latinos is a multi-site community-based cohort. At baseline (2008-2011), diet was assessed by using 2, 24-hour recalls. Shotgun sequencing was performed on stool samples collected in 2014-17 (n = 2444). Analysis of Compositions of Microbiomes 2 (ANCOM2) was used to identify the associations of dietary pattern scores with gut microbiome species and functions, adjusting for sociodemographic, behavioral, and clinical covariates. RESULTS: Better diet quality according to multiple healthy dietary patterns was associated with a higher abundance of species from class Clostridia, including [Eubacterium] eligens, Butyrivibrio crossotus, and Lachnospiraceae bacterium TF01-11, but functions related to better diet quality differed for the dietary patterns (e.g., aMED with pyruvate:ferredoxin oxidoreductase, hPDI with L-arabinose/lactose transport). Poorer diet quality was associated with a higher abundance of Acidaminococcus intestini and with functions of manganese/iron transport, adhesin protein transport, and nitrate reduction. Some healthy diet pattern-enriched Clostridia species were related to more favorable cardiometabolic traits such as lower triglycerides and waist-to-hip ratio. CONCLUSIONS: Healthy dietary patterns in this population are associated with a higher abundance of fiber-fermenting Clostridia species in the gut microbiome, consistent with previous studies in other racial/ethnic groups. Gut microbiota may be involved in the beneficial effect of higher diet quality on cardiometabolic disease risk.

Airflow obstruction is associated with cognitive dysfunction but studies have not assessed how emphysema, a structural phenotype of lung disease, might be associated with cognitive function independent from pulmonary function measured by spirometry. We aimed to determine the relationship between the presence of visually detectable emphysema on chest computed tomography (CT) imaging and cognitive function. We examined 2491 participants, mean age of 50 years, from the Coronary Artery Risk Development in Young Adults study who were assessed for the presence of emphysema on chest CT imaging and had cognitive function measured 5 years later with a battery of six cognitive tests. Of those assessed, 172 (7%) had emphysema. After adjusting for age, sex, height, study centre, race, body mass index, education and smoking, visual emphysema was significantly associated with worse performance on most cognitive tests. Compared to those without emphysema, participants with emphysema performed worse on cognitive testing: 0.39 sd units lower (95% CI -0.53- -0.25) on the Montreal Cognitive Assessment, 0.27 sd units lower (95% CI -0.42- -0.12) on the Rey Auditory Verbal Learning Test, 0.29 sd units lower (95% CI -0.43- -0.14) on the Digit Symbol Substitution Test and 0.25 sd units lower (95% CI -0.42- -0.09) on letter fluency. Further adjustment for forced expiratory volume in 1 s (FEV1), peak FEV1 and annualised FEV1 decline did not attenuate these associations. The presence of emphysema on chest CT is associated with worse cognitive function, independent of airflow obstruction. These data suggest that emphysema may be a novel risk factor for cognitive impairment.

Background

Genome-wide association studies (GWAS) have identified genetic factors in type 2 diabetes (T2D), mostly among individuals of European ancestry. We tested whether previously identified T2D-associated single nucleotide polymorphisms (SNPs) replicate and whether SNPs in regions near known T2D SNPs were associated with T2D within the Singapore Chinese Health Study.

Methods

2338 cases and 2339 T2D controls from the Singapore Chinese Health Study were genotyped for 507,509 SNPs. Imputation extended the genotyped SNPs to 7,514,461 with high estimated certainty (r(2)>0.8). Replication of known index SNP associations in T2D was attempted. Risk scores were computed as the sum of index risk alleles. SNPs in regions ± 100 kb around each index were tested for associations with T2D in conditional fine-mapping analysis.

Results

Of 69 index SNPs, 20 were genotyped directly and genotypes at 35 others were well imputed. Among the 55 SNPs with data, disease associations were replicated (at p<0.05) for 15 SNPs, while 32 more were directionally consistent with previous reports. Risk score was a significant predictor with a 2.03 fold higher risk CI (1.69-2.44) of T2D comparing the highest to lowest quintile of risk allele burden (p = 5.72 × 10(-14)). Two improved SNPs around index rs10923931 and 5 new candidate SNPs around indices rs10965250 and rs1111875 passed simple Bonferroni corrections for significance in conditional analysis. Nonetheless, only a small fraction (2.3% on the disease liability scale) of T2D burden in Singapore is explained by these SNPs.

Conclusions

While diabetes risk in Singapore Chinese involves genetic variants, most disease risk remains unexplained. Further genetic work is ongoing in the Singapore Chinese population to identify unique common variants not already seen in earlier studies. However rapid increases in T2D risk have occurred in recent decades in this population, indicating that dynamic environmental influences and possibly gene by environment interactions complicate the genetic architecture of this disease.