Developing a Theory-Based Instrument for Pre-Exposure Prophylaxis (PrEP) Uptake in People of Color Using a Qualitative Approach.

There is a large disparity in Pre-exposure Prophylaxis (PrEP) utilization among communities of color compared to White Americans. There is also a lack of theory-based survey instruments to measure the underlying reasons for the disparity among communities of color. The purpose of this study was to create an instrument based on a qualitative approach involving community interviews. Semi-structured interviews guided by the Multi-theory Model (MTM) of health behavior change were performed in a sample of 12 members from communities of color. The analysis entailed a directed content analysis along the themes of MTM constructs to develop a survey instrument. The barriers to PrEP that emerged included the cost of PrEP, lack of protection from other sexually transmitted diseases, reduced trust between partners, and the stigma associated with PrEP. The perceived disadvantages included the potential cost of PrEP, partner mistrust when taking PrEP, discussion of sexual behaviors with a provider, and unclear process of acquiring the PrEP prescription. The results guided the development of a survey tool to further investigate aspects of cost, partner relations, stigma, reassurance of safety, and other factors. The tool can be used for future studies as part of guided interventions to increase PrEP uptake.

Theory-based antecedents of breastfeeding among pregnant women in the United States.

Background: Breastfeeding provides several positive health benefits for the newborn child, yet breastfeeding rates remain low in the United States (US). Theory-based approaches have the potential to improve breastfeeding promotion interventions. Hence, the study examined the correlates of intention to breastfeed among US pregnant women based on the multi-theory model (MTM) of health behavior change. Methods: Using a cross-sectional design, a 36-item online survey was administered to a nationally representative sample of 315 pregnant women in the US. The instrument was psychometrically validated for face, content, and construct validity by a panel of six experts over two rounds. Further, construct validation was done by confirmatory factor analysis (CFA). Hierarchical regression modeling was employed to explain the intention to start breastfeeding and sustain exclusive breastfeeding for up to six months and with complementary foods for up to 24 months. Results: Internal consistency using Cronbach's alpha was found to be acceptable. It was found that behavioral confidence and changes in the physical environment positively affected the initiation of breastfeeding (P<0.01; adjusted R2=0.478). All three constructs of MTM namely practice for change, emotional transformation, and changes in the social environment were significant predictors for the sustenance of breastfeeding at six months (P<0.01; adjusted R2=0.591) and at 24 months (P<0.01; adjusted R2=0.347). Conclusion: Based on the findings of this study it is essential for educators and healthcare providers to design MTM-based interventions to promote breastfeeding among pregnant women in the US.

Explaining the Correlates of Eating Outside-of-Home Behavior in a Nationally Representative US Sample Using the Multi-Theory Model of Health Behavior Change: A Cross-Sectional Study.

Eating outside-of-home (EOH) is one of the main changes in lifestyle that occurred worldwide in the past few decades. Given that EOH behavior is influenced by individual and contextual factors, the utilization of a theory seems to be suitable in analyzing this health behavior. The fourth-generation theory multi-theory model (MTM) is designed exclusively for health behavior change at the individual and community levels. Therefore, the purpose of this analytical cross-sectional study was to investigate EOH behavior by using the MTM among a nationally representative sample in the United States (US). Data for this study were collected from April-May 2023 via a 61-item psychometric valid, web-based, structured survey disseminated via Qualtrics. Chi-square/Fisher's exact tests were used to compare categorical data, whereas the independent-samples t-test was used to compare the mean scores of MTM constructs across groups. Pearson correlation analysis was performed for the intercorrelation matrix between the MTM constructs and hierarchical regression models were built to predict the variance in the initiation and sustenance by certain predictor variables beyond demographic characteristics. The p values in the multiple comparisons were calculated by using adjusted residuals. Among a total of 532 survey respondents, 397 (74.6%) indicated being engaged in EOH at least twice a week, whereas 135 (25.4%) reported not being engaged in EOH. People who were engaged in EOH were younger (mean age = 42.25 ± 17.78 years vs. 55.89 ± 19.43 years) African American, (15.9% vs. 6.7%, p = 0.01), single or never married, (34.0% vs. 23.0%, p = 0.02), had a graduate degree (9.6% vs. 3.7%, p = 0.03), and were employed (72.0% vs. 34.8%, p < 0.001) as opposed to those who reported not being engaged in eating outside the home. Among the MTM constructs of initiation, "behavioral confidence" and "changes in the physical environment" were the significant predictors of initiating a reduction in EOH behavior and explained 48% of the variance in initiation. Among the MTM constructs of sustenance, "emotional transformation" and "changes in the social environment" were the significant predictors of sustaining a reduction in EOH behavior and explained 50% of the variance in sustenance. This study highlights a need to design MTM-based educational interventions that promote in-home eating instead of frequent EOH for health, family bonding, economic, and other reasons.

Using the Multi-Theory Model (MTM) of Health Behavior Change to Explain the Seeking of Stool-Based Tests for Colorectal Cancer Screening.

Colorectal cancer is the third most common cancer worldwide and is the second leading cause of cancer-associated deaths. While colorectal cancer is on the decline in the United States (US), disparities still exist, despite the non-invasive screening modalities, such as stool-based tests have shown themselves to be effective in the detection of colorectal cancer. Many of the existing stool-based test interventions lack the use of a contemporary theory-based approach. Given the paucity of theory-based interventions intended to promote stool-based tests, this cross-sectional study utilizes the multi-theory model (MTM) of health behavior change to explain the seeking of stool-based tests for colorectal cancer (CRC) screening. An online 57-item questionnaire with an established psychometric validity was used to collect responses from the US-based sample (n = 640) of adults aged 45-75 years old. The data were analyzed using bivariate and multivariate statistical methods. Structural equation modeling (SEM) was conducted to test the construct validity of the survey instrument. In this nationwide sample, 39.2% (n = 251) of participants reported having received some form of a stool-based test. Among the participants who did not undergo stool-based CRC screening, the MTM subscales, including "participatory dialogue", "behavioral confidence", and "changes in the social environment", were significant predictors of initiating screening behavior and explained 48% of the variance in the initiation among this group (R2 = 0.579, F = 5.916, p < 0.001; adjusted R2 = 0.481). The MTM may be a useful framework with which to design educational, mass media, social media, and clinical interventions for the promotion of stool-based CRC screening among adults aged 45-75 years old.

Explaining Correlates of Cervical Cancer Screening among Minority Women in the United States.

Globally, cervical cancer is the fourth leading cause of death among women. While overall cervical cancer rates have decreased over the last few decades, minority women continue to be disproportionately affected compared to White women. Given the paucity of theory-based interventions to promote Pap smear tests among minority women, this cross-sectional study attempts to examine the correlates of cervical cancer screening by Pap test using the Multi-theory Model (MTM) as a theoretical paradigm among minority women in the United States (U.S.). Structural Equation Modelling (SEM) was done for testing the construct validity of the survey instrument. Data were analyzed through bivariate and multivariate tests. In a sample of 364 minority women, nearly 31% (n = 112) of women reported not having received a Pap test within the past three years compared to the national rate (20.8%) for all women. The MTM constructs of participatory dialogue, behavioral confidence, and changes in the physical environment explained a substantial proportion of variance (49.5%) in starting the behavior of getting Pap tests, while the constructs of emotional transformation, practice for change, and changes in the social environment, along with lack of health insurance and annual household income of less than $25,000, significantly explained the variance (73.6%) of the likelihood to sustain the Pap test behavior of getting it every three years. Among those who have had a Pap smear (n = 252), healthcare insurance, emotional transformation, practice for change, and changes in the social environment predicted nearly 83.3% of the variance in sustaining Pap smear test uptake behavior (adjusted R2 = 0.833, F = 45.254, p < 0.001). This study validates the need for health promotion interventions based on MTM to be implemented to address the disparities of lower cervical cancer screenings among minority women.

Exploring mediation pathways on the relationship between acculturation and binge eating among Latino adolescents.

The objective of this study was to explore the mediating effects of emotional eating, restrained eating, and external eating on the relationship between acculturation and binge eating among Latino adolescents. Adolescents who self-identified as Latino (N = 285) at public high schools in Southern California were recruited and completed a self-report survey. Acculturation was assessed using the 8-item Acculturation, Habits, Interests for Multicultural Adolescents (AHIMSA) scale for adolescents, mediators were assessed using Dutch Eating Behavior Questionnaire (DEBQ), and binge eating was assessed using a 13-item Eating Disorder Diagnostic Scale. A bootstrapped multiple mediation model was used to test mediation pathways. Findings suggest that individually each eating style-emotional, restrained and external eating pathway did not reach significance singly, but that jointly, their combined effect was significant with a total indirect effect (B = 0.15, CI 0.01-0.30) indicating an additive effect of the three eating styles. Future research should examine additional mediators of the relationship between acculturation and binge eating.

Exploring Potential Mediation Pathways on the Relationship Between Acculturation and Body Mass Index (BMI) Among Latino Adolescents.

BACKGROUND: Positive associations have been observed between acculturation and body mass index (BMI), but the mediators of this relationship are not well established. Acculturation researchers have called for investigating the influence of socio-contextual variables as mediators. The objective of this study was to test the mediating effects of salty snacks, sweet snacks, physical activity, and sedentary behavior on the relationship between acculturation and BMI among Latino adolescents. METHODS: Adolescents who self-identified as Latino (n = 431) at public high schools in Southern California were recruited and completed a self-report survey. A bootstrapped multiple mediation model was used to test mediation pathways. RESULTS: Acculturation was positively associated with physical activity (B = 0.09, p < .05). The indirect effects of salty snacks, sweet snacks, physical activity, and sedentary behavior were not associated with BMI, suggesting no mediation. CONCLUSIONS: Future research should examine additional mediating variables on the relationship between acculturation and BMI.

Threshold score for the self-report Pediatric Distress Thermometer Rating Scale in childhood cancer patients.

OBJECTIVE: Although there is enthusiasm for identifying and treating psychosocial problems in childhood cancer patients, there are few validated instruments to help providers identify at-risk children for further assessment. The study objective was to evaluate the sensitivity and specificity of the self-report pediatric Distress Thermometer Rating Scale (Peds DTRS) in childhood cancer survivors and identify a threshold score to help providers classify pediatric patients. METHODS: We evaluated 54 children 7-17 years old using 178 Peds DTRS longitudinal data points from the cohort that was used for the original pediatric adaptation of the DTRS. We compared Peds DTRS scores against two established standardized measures using a generalized linear mixed model to deal with the dependency in the longitudinal data to estimate ROC curves and related statistics. RESULTS: Results indicate that a score of 3 is a reasonable cutoff to identify distress with children 7-17 years old. This cutoff yielded high sensitivity (87.0%) and specificity (79.7%) using the PedsQL Emotional Domain score as the standard. Similar results were obtained using the CDI as the standard, but we are cautious as very few CDI scores reached the cutoff criterion. Exploratory analysis highlighted clinical factors that correlate with increased distress measured using the Peds DTRS. CONCLUSIONS: The Peds DTRS is a very brief, convenient, and rapid screening tool for global distress in children. Further investigation of the Peds DTRS and other tools can improve the ability of providers to prevent and treat the negative emotional consequences of cancer and improve the quality of survivorship.

Social-ecological predictors of school functioning in Hispanic children treated for cancer with central nervous system-directed therapies.

BACKGROUND: Children with brain tumor or acute leukemia are at risk for neurotoxic side effects associated with their cancer therapies. These long-term deficits include poor health-related quality of life (HRQOL) in school and lower educational achievement. Although social-ecological factors may impact these outcomes, it is not known which factors play a role. Our objective was to evaluate the factors affecting school HRQOL in Hispanic childhood cancer survivors, an important at-risk group. PROCEDURE: Multivariable regression analyses examined whether selected social-ecological factors contribute toward suboptimal school HRQOL in 73 Hispanic children treated with central nervous system (CNS)-directed cancer therapies after accounting for effects associated with established cancer-related risk factors. RESULTS: Consistent with expectations from prior research, in our multivariate analysis, the cancer-related factors of having a brain tumor diagnosis and being younger at cancer diagnosis were significant predictors of reduced parent-reported school HRQOL (F(2,65) = 5.46, P < .01) and accounted for 14% of the variance. Adding the social-ecological variables of parent education, child motivation, and parental knowledge accounted for an additional 25% of the variance in school HRQOL, where higher levels were associated with better child school HRQOL. Parenting knowledge was a contributor even after controlling for effects associated with the other variables in the model (F(1,62) = 4.88, P < .05). CONCLUSIONS: Cancer survivorship care should incorporate parent education interventions to enhance the child's school functioning, particularly for Hispanic childhood cancer survivors from predominantly Spanish-speaking families. Future research should consider other at-risk groups and incorporate social-ecological indicators to predict HRQOL outcomes.

An Examination of Family Variables as Mediators of the Association of Acculturation With Sugar-Sweetened Beverage Consumption Among Latinx Adolescents.

The objective of this study was to examine the mediating effects of family support for dietary habits and family meal frequency on the relationship between acculturation and sugar-sweetened beverage (SSB) consumption among Latinx adolescents (N = 131). Acculturation was positively associated with SSB consumption (B = 0.07, P < .01). Results suggest that family support for dietary habits and family meal frequency did not mediate the relationship between acculturation and SSB consumption. However, acculturation was negatively associated with family support for dietary habits (B = -0.10, P < .01) and family meal frequency (B = -0.11, P < .05). Future research should examine other family influences as mediators of the relationship between acculturation and SSB consumption.

The Association of Trail Features With Self-Report Trail Use by Neighborhood Residents.

BACKGROUND: Urban trails are a useful resource to promote physical activity. This study identified features of urban trails that correlated with trail use. METHODS: Multiuse urban trails were selected in Chicago, Dallas, and Los Angeles. An audit of each trail was completed using the Systematic Pedestrian and Cyclist Environmental Scan for Trails instrument, identifying built environmental features. A self-report of trail use was obtained from trailside residents (N = 331) living within 1 mile of each trail. Univariate and multivariate Poisson regressions controlled for trail time from home and motivation for physical activity. RESULTS: Positive associations with the past month's hours on the trail were observed for the presence of distance signs, vegetation height, vegetation maintenance, and trail crowding, and a negative association was observed for the presence of crossings on the trail. Positive associations with dichotomous trail use were observed for the presence of distance signs, vegetation height, and vegetation maintenance, and a negative association was observed for the presence of crossings on the trail. CONCLUSIONS: These correlates should be confirmed in other studies and, if supported, should be considered in the promotion and design of urban trails.

Acculturation and sugar-sweetened beverage consumption among Hispanic adolescents: The moderating effect of impulsivity.

Consumption of sugar-sweetened beverages is a risk factor for obesity. Acculturation to the United States (US) might increase sugar-sweetened beverage consumption among Hispanic adolescents, but few moderators of this relationship have been examined. This study examined the moderating influence of impulsivity on the association between acculturation and sugar-sweetened beverages. Hispanic adolescents (n = 154), 14-17 years, were identified and screened for eligibility through low-SES high schools and parents provided consent. Adolescents completed measures of acculturation using Unger's 8-item acculturation scale, impulsivity, and diet. Multiple linear regression was used to examine the main effect of acculturation and the interaction of acculturation with impulsivity on the diet outcomes: sugar-sweetened beverage consumption and percent of calories from sugar. Acculturation was positively associated with sugar-sweetened beverages (ß = 0.43; p < .05). The interaction of acculturation x impulsivity was significant (ß = 0.42, p < .05). Among youth who were more acculturated, those who were more impulsive consumed more sugar-sweetened beverages. Youth who were more acculturated, but less impulsive consumed less sugar-sweetened beverages. Neurocognitive variables such as impulsivity may be important moderators of the influence of acculturation on dietary behavior. Targeted messaging strategies based on levels of acculturation and impulsivity might enhance the effectiveness of interventions designed to reduce the intake of sugar-sweetened beverages among Hispanic adolescents.

Targeted exonic sequencing of GWAS loci in the high extremes of the plasma lipids distribution.

OBJECTIVE: Genome-wide association studies (GWAS) for plasma lipid levels have mapped numerous genomic loci, with each region often containing many protein-coding genes. Targeted re-sequencing of exons is a strategy to pinpoint causal variants and genes. METHODS: We performed solution-based hybrid selection of 9008 exons at 939 genes within 95 GWAS loci for plasma lipid levels and sequenced using next-generation sequencing technology individuals with extremely high as well as low to normal levels of low-density lipoprotein cholesterol (LDL-C, n = 311; mean low = 71 mg/dl versus high = 241 mg/dl), triglycerides (TG, n = 308; mean low = 75 mg/dl versus high = 1938 mg/dl), and high-density lipoprotein cholesterol (HDL-C, n = 684; mean low = 32 mg/dl versus high = 102 mg/dl). We identified 15,002 missense, nonsense, or splice site variants with a frequency <5%. We tested whether coding sequence variants, individually or aggregated within a gene, were associated with plasma lipid levels. To replicate findings, we performed sequencing in independent participants (n = 6424). RESULTS: Across discovery and replication sequencing, we found 6 variants with significant associations with plasma lipids. Of these, one was a novel association: p.Ser147Asn variant in APOA4 (14.3% frequency, TG OR = 0.49, P = 7.1 × 10(-4)) with TG. In gene-level association analyses where rare variants within each gene are collapsed, APOC3 (P = 2.1 × 10(-5)) and LDLR (P = 5.0 × 10(-12)) were associated with plasma lipids. CONCLUSIONS: After sequencing genes from 95 GWAS loci in participants with extremely high plasma lipid levels, we identified one new coding variant associated with TG. These results provide insight regarding design of similar sequencing studies with respect to sample size, follow-up, and analysis methodology.

Common low-density lipoprotein receptor p.G116S variant has a large effect on plasma low-density lipoprotein cholesterol in circumpolar inuit populations.

BACKGROUND: Inuit are considered to be vulnerable to cardiovascular disease because their lifestyles are becoming more Westernized. During sequence analysis of Inuit individuals at extremes of lipid traits, we identified 2 nonsynonymous variants in low-density lipoprotein receptor (LDLR), namely p.G116S and p.R730W. METHODS AND RESULTS: Genotyping these variants in 3324 Inuit from Alaska, Canada, and Greenland showed they were common, with allele frequencies 10% to 15%. Only p.G116S was associated with dyslipidemia: the increase in LDL cholesterol was 0.54 mmol/L (20.9 mg/dL) per allele (P=5.6×10(-49)), which was >3× larger than the largest effect sizes seen with other common variants in other populations. Carriers of p.G116S had a 3.02-fold increased risk of hypercholesterolemia (95% confidence interval, 2.34-3.90; P=1.7×10(-17)), but did not have classical familial hypercholesterolemia. In vitro, p.G116S showed 60% reduced ligand-binding activity compared with wild-type receptor. In contrast, p.R730W was associated with neither LDL cholesterol level nor altered in vitro activity. CONCLUSIONS: LDLR p.G116S is thus unique: a common dysfunctional variant in Inuit whose large effect on LDL cholesterol may have public health implications.

Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk for myocardial infarction.

Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance. When MI occurs early in life, genetic inheritance is a major component to risk. Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk in individual families, whereas common variants at more than 45 loci have been associated with MI risk in the population. Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (≤50 years in males and ≤60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol. Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.

LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias.

We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients with a range of phenotypes including extreme blood lipid concentrations as well as additional dyslipidemias and related metabolic disorders. The panel performs well, with high concordance (95.2%) in samples with known mutations based on Sanger sequencing and a high detection rate (57.9%) of mutations likely to be causative for disease in samples not previously sequenced. Clinical implementation of LipidSeq has the potential to aid in the molecular diagnosis of patients with monogenic dyslipidemias with a high degree of speed and accuracy and at lower cost than either Sanger sequencing or whole exome sequencing. Furthermore, LipidSeq will help to provide a more focused picture of monogenic and polygenic contributors that underlie dyslipidemia while excluding the discovery of incidental pathogenic clinically actionable variants in nonmetabolism-related genes, such as oncogenes, that would otherwise be identified by a whole exome approach, thus minimizing potential ethical issues.

Patient outcomes in canceled MRI-guided breast biopsies.

OBJECTIVE: The reported frequency of aborted MRI-guided breast biopsies ranges from 8% to 17%, usually secondary to nonvisualization at attempted biopsy. Our study examines the frequency of MRI-guided breast biopsies aborted because of lesion nonvisualization and the subsequent risk of malignancy. MATERIALS AND METHODS: We identified 350 patients and 445 lesions scheduled for MRI-guided biopsy between January 1, 2007, and December 31, 2009. Medical records and imaging studies were reviewed to ascertain patient demographics, lesion and imaging characteristics, and subsequent pathology results. Chi-square statistics were calculated for patient level analyses. RESULTS: MRI-guided biopsies were aborted in 13% (56/445) of lesions and 15% (53/350; 95% CI, 11.6-19.3%) of patients because of nonvisualization of the biopsy target at the time of attempted biopsy. Of these 53 patients, 50 patients had follow-up data available. Malignancy was subsequently diagnosed in five of those 50 patients (10%; 95% CI, 3.3-21.8%), three with invasive ductal carcinomas and two with ductal carcinoma in situ. The mean time to malignant diagnosis from the date of aborted biopsy was 2.6 months (range, 1.1-6.9 months). CONCLUSION: Informed consent for MRI-guided breast biopsies should include discussion of biopsy cancellation because of nonvisualization of the target lesion. The low yet significant risk of malignancy in patients subsequent to an aborted MRI-guided breast biopsy warrants short-term follow-up MRI after a canceled biopsy.

Western Database of Lipid Variants (WDLV): a catalogue of genetic variants in monogenic dyslipidemias.

BACKGROUND: Next-generation sequencing (NGS) is nearing routine clinical application, especially for diagnosis of rare monogenic cardiovascular diseases. But NGS uncovers so much variation in an individual genome that filtering steps are required to streamline data management. The first step is to determine whether a potential disease-causing variant has been observed previously in affected patients. METHODS: To facilitate this step for lipid disorders, we developed the Western Database of Lipid Variants (WDLV) of 2776 variants in 24 genes that cause monogenic dyslipoproteinemias, including conditions characterized primarily by either high or low low-density lipoprotein cholesterol, high or low high-density lipoprotein cholesterol, high triglyceride, and some miscellaneous disorders. We incorporated quality-control steps to maximize the likelihood that a listed mutation was disease causing. RESULTS: The details of each mutation found in a dyslipidemia, together with a mutation map of the causative genes, are shown in graphical display items. CONCLUSIONS: WDLV will help clinicians and researchers determine the potential pathogenicity of mutations discovered by DNA sequencing of patients or research participants with lipid disorders.

Genetic determinants of "cognitive impairment, no dementia".

Dementia is a heritable condition with devastating effects on both patients and their caregivers. Studies have identified genetic variants associated with increased susceptibility to late-onset Alzheimer disease (AD)-related dementia; however, no studies have assessed whether genetic variation is associated with the early stages of cognitive decline. Given that cerebrovascular disease is an established mechanism in which chronic ischemia increases susceptibility to dementia, we assessed whether genetic variation associated with either cardio-metabolic or AD-related traits is associated with an early stage of cognitive decline called "cognitive impairment, no dementia" (CIND). We studied 484 CIND patients and 459 cognitively healthy controls selected from the Canadian Study of Health and Aging. We tested for association between ~200,000 genetic variants selected from genes associated with cardio-metabolic traits and CIND status using the Cardio-MetaboChip. We also assessed whether AD-related variants and APOE alleles were associated with CIND status, either individually or as part of a composite genetic risk score. We identified a potential association between the ZNF608/GRAMD3 locus, specifically the rs1439568 polymorphism and CIND status (major allele odds ratio [OR] = 1.51; p = 8.4 × 10(-6)). AD-related variants were not associated with CIND status, however APOE E4 allele frequency was significantly higher in CIND patients versus healthy controls (OR = 1.35; p = 0.044). We identified a potential association between the ZNF608/GRAMD3 locus and CIND status, although AD-related variants were not associated with CIND. Additional replication of this association signal is invited.

The complex genetic basis of plasma triglycerides.

Demonstration of a direct relationship between plasma triglyceride (TG) concentration and atherosclerosis has proven difficult due to confounding variables that accompany elevated plasma TG, such as other dyslipidemias, obesity, and type 2 diabetes. However, human genetic studies have provided evidence suggesting a causal link between plasma TG and cardiovascular risk. Analyses in human patients with hypertriglyceridemia (HTG) also provides insight into the relationship between genetic variation, predisposition to elevated plasma TG, and risk of subsequent cardiovascular disease. Here, we review recent key studies that have contributed to our understanding of the genetic determinants of plasma TG concentration, including HTG susceptibility and phenotypic heterogeneity, and discuss our maturing model of the allelic and phenotypic spectrum of plasma TG.