Internal heating method of loop-mediated isothermal amplification for detection of HPV-6 DNA.

Loop-mediated isothermal amplification (LAMP) is a promising diagnostic tool for genetic amplification, which is known for its rapid process, simple operation, high amplification efficiency, and excellent sensitivity. However, most of the existing heating methods are external for completion of molecular amplification with possibility of contamination of specimens. The present research provided an internal heating method for LAMP using magnetic nanoparticles (MNPs), which is called nano-LAMP. Near-infrared light with an excitation wavelength of 808 nm was employed as the heating source; hydroxy naphthol blue (HNB) was used as an indicator to conduct methodological research. We demonstrate that the best temperature was controlled at a working power of 2 W and 4.8 µg/µL concentration of nanoparticles. The lowest limit for the detection of HPV by the nano-LAMP method is 102 copies/mL, which was confirmed by a gel electrophoresis assay. In the feasibility investigation of validated clinical samples, all 10 positive HPV-6 specimens amplified by nano-LAMP were consistent with conventional LAMP methods. Therefore, the nano-LAMP detection method using internal heating of MNPs may bring a new vision to the exploration of thermostatic detection in the future.

HIV Integrase Inhibitor Pharmacogenetics: An Exploratory Study.

BACKGROUND AND OBJECTIVES: Integrase strand transfer inhibitors (INSTIs), dolutegravir, elvitegravir, and raltegravir, have become integral in the treatment of HIV, with close monitoring of continued efficacy and tolerability. As side effect occurrence varies among subjects receiving these drugs, we sought to perform an exploratory analysis examining the role of several single-nucleotide polymorphisms (SNPs) on drug concentration changes, selected clinical outcomes, and the occurrence of subject-reported adverse events. METHODS: Adults (aged ≥ 18 years) receiving INSTI-based regimens for treatment of HIV were recruited and genotyped with an iPLEX ADME PGx Pro v1.0 Panel. Multiple linear or logistic regression with covariates [age, sex, BMI, regimen (in the across-regimen group), regimen duration, and baseline variables (for continuous parameters)] was used to detect significant (p < 0.05) association of selected clinical data with genetic variants within the study population. RESULTS: In a sample (n = 88) with a median age of 52.5 years (IQR 45.7-57.2) being predominately Caucasian (88.6%) and male (86.4%), this exploratory study discovered several associations between variables and SNPs, when using INSTIs. Abnormal dream occurrence was statistically different (p = 0.028) between regimens. Additionally, several SNPs were found to be associated with adverse event profiles primarily when all regimens were grouped together. CONCLUSION: The associations found in this study point to a need for further assessment, within the population living with HIV, of factors contributing to unfavorable subject outcomes. These exploratory findings require confirmation in larger studies, which then may investigate pharmacogenetic mechanisms.

Health Care Provider Intervention and Utilization of Cessation Assistance in 12 Low- and Middle-Income Countries.

Background and Aim: There is a need to improve utilization of cessation assistance in low- and middle-income countries (LMICs), and tobacco cessation research has been identified as priority in LMICs. This study evaluates the relationship between health care provider intervention and cessation assistance utilization in LMICs. Methods: Data from 13 967 participants (aged ≥15 years, 90.3% males) of the Global Adults Tobacco Survey conducted in 12 LMICs (74.3%-97.3% response rates) were analyzed with utilization of counseling/cessation clinic, WHO-recommended medications, and quitline as outcome variables. Health care provider intervention ("no intervention," only "tobacco screening," "quit advice") was the exposure variable. Weighted multiple logistic regression models were used to examine the relationship between each outcome variable and the exposure variable, adjusting for other covariates. Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) are reported. Results: Approximately 52%, 8%, and 40% of participants received no intervention, only tobacco screening, and advice to quit, respectively. Overall, 0.4%, 1.9%, 3.0%, and 4.5% used quitline, WHO-recommended medications, counseling/cessation clinic, and any cessation assistance, respectively. Compared with no intervention, quit advice was associated with increased utilization of quitline (OR = 2.24, 95% CI = 1.2 to 4.4), WHO-recommended medications (OR = 1.67, 95% CI = 1.2 to 2.3), counseling/cessation clinic (OR = 4.41, 95% CI = 3.2 to 6.1), and any assistance (any of the three types) (OR = 2.80, 95% CI = 2.2 to 3.6). Conclusion: The findings of this study suggest that the incorporation of quit advice by health care providers in tobacco control programs and health care systems in LMICs could potentially improve utilization of cessation assistance to improve smoking cessation in LMICs. Implications: This first study of association between health care provider intervention and the utilization of cessation assistance in LMICs reports that there was a missed opportunity to provide quit advice to about 60% of smokers who visited a health care provider in the past year. The odds of utilization of counseling/cessation clinic, WHO-recommended medications, and quitline were significantly increased in participants who were advised to quit smoking. The results suggest that effective integration and implementation of advice to quit in tobacco control programs and the national health care systems may increase the use of cessation assistance to quit smoking.

Polymorphisms Within RYR3 Gene Are Associated With Risk and Age at Onset of Hypertension, Diabetes, and Alzheimer's Disease.

BACKGROUND: Hypertension affects 33% of Americans while type 2 diabetes and Alzheimer's disease (AD) affect 10% of Americans, respectively. Ryanodine receptor 3 gene (RYR3) codes for the RYR which functions to release stored endoplasmic reticulum calcium ions (Ca2+) to increase intracellular Ca2+ concentration. Increasing studies demonstrate that altered levels of intracellular Ca2+ affect cardiac contraction, insulin secretion, and neurodegeneration. In this study, we investigated associations of the RYR3 genetic variants with hypertension, AD, and diabetes. METHODS: Family data sets were used to explore association of RYR3 polymorphisms with risk and age at onset (AAO) of hypertension, diabetes, and AD. RESULTS: Family-based association tests using generalized estimating equations (FBAT-GEE) showed several unique or shared disease-1 associated variants in the RYR3 gene. Three single nuclear polymorphisms (SNPs; rs2033610, rs2596164, and rs2278317) are significantly associated with risk for hypertension, diabetes, and AD. Two SNPs (rs4780174 and rs7498093) are significantly associated with AAO of the 3 diseases. CONCLUSIONS: RYR3 variants are associated with hypertension, diabetes, and AD. Replication of these results of this gene in these 3 complex traits may help to better understand the genetic basis of calcium-signaling gene, RYR3 in association with risk and AAO of these diseases.

Analysis of PTPRK polymorphisms in association with risk and age at onset of Alzheimer's disease, cancer risk, and cholesterol.

The human receptor-type protein-tyrosine phosphatase kappa (PTPRK) gene is highly expressed in human brain and was previously associated with an increased risk of neuropsychiatric disorders and cancer. This study investigated the association of 52 single nucleotide polymorphisms (SNPs) in PTPRK with the risk and age at onset (AAO) of Alzheimer's disease (AD) in 791 AD patients and 782 controls. Our data analysis showed that five SNPs (top SNP rs4895829 with p = 0.0125) were associated with the risk of AD based on a multiple logistic regression (p < 0.05); while six SNPs (top SNP rs1891150 with p = 8.02 × 10-6) were associated with AAO by using a multiple linear regression analysis. Interestingly, rs2326681 was associated with both the risk and AAO of AD (p = 4.65 × 10-2 and 5.18 × 10-3, respectively). In a replication study, the results from family-based association test - generalized estimating equation (GEE) statistics and Wilcoxon test showed that seven SNPs were associated with the risk of AD (top SNP rs11756545 with p = 1.02 × 10-2) and 12 SNPs were associated with the AAO (top SNP rs11966128 with p = 1.39 × 10-4), respectively. One additional sample showed that four SNPs were associated with risk of cancer (top SNP rs1339197 with p = 4.1 × 10-3), 12 SNPs associated with LDL-cholesterol (top SNP rs4544930 with p = 3.47 × 10-3), and eight SNPs associated with total cholesterol (top SNP rs1012049 with p = 6.09 × 10-3). In addition, the AD associated rs4895829 was associated with the gene expression level in the cerebellum (p = 7.3 × 10-5). The present study is the first study providing evidence of several genetic variants within the PTPRK gene associated with the risk and AAO of AD, risk of cancer, LDL and total cholesterol levels.

Generalized Linear Mixed Model Analysis of Urban-Rural Differences in Social and Behavioral Factors for Colorectal Cancer Screening

Objective: Screening for colorectal cancer (CRC) can reduce disease incidence, morbidity, and mortality. However, few studies have investigated the urban-rural differences in social and behavioral factors influencing CRC screening. The objective of the study was to investigate the potential factors across urban-rural groups on the usage of CRC screening. Methods: A total of 38,505 adults (aged ≥40 years) were selected from the 2009 California Health Interview Survey (CHIS) data - the latest CHIS data on CRC screening. The weighted generalized linear mixed-model (WGLIMM) was used to deal with this hierarchical structure data. Weighted simple and multiple mixed logistic regression analyses in SAS ver. 9.4 were used to obtain the odds ratios (ORs) and their 95% confidence intervals (CIs). Results: The overall prevalence of CRC screening was 48.1% while the prevalence in four residence groups - urban, second city, suburban, and town/rural, were 45.8%, 46.9%, 53.7% and 50.1%, respectively. The results of WGLIMM analysis showed that there was residence effect (p<0.0001) and residence groups had significant interactions with gender, age group, education level, and employment status (p<0.05). Multiple logistic regression analysis revealed that age, race, marital status, education level, employment stats, binge drinking, and smoking status were associated with CRC screening (p<0.05). Stratified by residence regions, age and poverty level showed associations with CRC screening in all four residence groups. Education level was positively associated with CRC screening in second city and suburban. Infrequent binge drinking was associated with CRC screening in urban and suburban; while current smoking was a protective factor in urban and town/rural groups. Conclusions: Mixed models are useful to deal with the clustered survey data. Social factors and behavioral factors (binge drinking and smoking) were associated with CRC screening and the associations were affected by living areas such as urban and rural regions.

Family-based association analysis of NAV2 gene with the risk and age at onset of Alzheimer's disease.

The neuron navigator 2 (NAV2) gene is highly expressed in brain and involved in the nervous system development and may play a role in Alzheimer's disease (AD). We aimed to investigate the associations of 317 single-nucleotide polymorphisms (SNPs) in the NAV2 gene with the risk and age at onset (AAO) of AD using a family-based sample (1266 AD cases and 1279 healthy relatives). Association with the risk of AD was assessed using family-based association test -generalized estimating equations (FBAT- GEE) statistics while the association with AAO as a quantitative trait was evaluated using the FBAT-Wilcoxon statistic. Single marker analysis showed that 20 SNPs were significantly associated with the risk of AD (top SNP rs7112354 with p=8.46×10-4) and 11 SNPs were associated with AAO (top SNP rs1354269 with p=2.87×10-3). Interestingly, two SNPs rs17614100 and rs12364788 were associated with both the risk (p=1.7×10-2 and 2.71×10-2; respectively) and AAO (p=1.85×10-3 and 6.06×10-3; respectively). Haplotype analyses further supported the results of single marker analyses. In addition, functional analysis showed that NAV2 mRNA had significant expression across ten human brain regions examined and significantly correlated with APOE expression in four of ten regions. The present study is the first study providing evidence of several genetic variants within the NAV2 gene influencing the risk and AAO of AD.

Intentions to quit tobacco smoking in 14 low- and middle-income countries based on the transtheoretical model.

INTRODUCTION: Over 80% of the world's one billion tobacco smokers reside in low- and middle-income countries (LMICs); therefore, it is important to understand factors that promote intention to quit smoking in these countries. This study evaluated factors associated with three stages of intention to quit tobacco smoking among adults in LMICs. METHODS: Data from 43,540 participants of the Global Adult Tobacco Survey in 14 LMICs were analyzed. Intentions to quit smoking were categorized into precontemplation (referent category), contemplation, and preparation stages based on the transtheoretical model. A multinomial logit model was used to estimate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Approximately 82%, 14%, and 4% of the smokers were in precontemplation, contemplation, and preparation stages, respectively. Rural residents had increased odds of being in contemplation stage (OR=1.41, 95% CI=1.09-1.83) compared to urban residents. Compared to homes where smoking was allowed, smoke-free homes were associated with increased odds of contemplation (OR=1.77, 95% CI=1.41-2.23) and preparation (OR=2.18, 95% CI=1.78-2.66). Exposure to anti-smoking messages in more than one media channel was associated with increased odds of contemplation (OR=1.60, 95% CI=1.33-1.92) and preparation (OR=1.73, 95% CI=1.28-2.33) compared to no exposure to anti-smoking messages. CONCLUSION: The results suggest that anti-smoking media campaigns and smoke-free policies may promote intention to quit smoking in LMICs. While these suggest the need for implementation of comprehensive anti-smoking campaigns and smoke-free policies, longitudinal studies are required to confirm these findings and to evaluate how intention to quit translates into quit attempts in LMICs.

Sleep duration and smoking are associated with coronary heart disease among US adults with type 2 diabetes: Gender differences.

AIMS: The associations of moderate alcohol consumption, sleep duration, and tobacco smoking with coronary heart disease (CHD) among patients with type 2 diabetes mellitus (T2D) are not clearly clarified. The aims of the study were to evaluate the associations of lifestyle factors, hypertension, obesity, depression and sleep duration with CHD development among patients with T2D, and particularly, to examine the gender differences in risk factors for CHD. METHODS: A total of 2335 T2D adults were selected from the 2012 National Health Interview Survey. Weighted univariate and multiple logistic regression analyses were used to estimate the odds ratios with 95% confidence intervals. RESULTS: The CHD prevalence among patients with T2D was 14.2% (18.1% and 10.4% for males and females, respectively), which increased with age (10.3% and 19.6% for age groups 18-64 and 65+, respectively). After adjusting for other factors, weighted logistic regression analyses showed that CHD among patients with T2D was significantly associated with being male, older age, past smoking, long sleep duration, hypertension, and high cholesterol level. Furthermore, the significant association of older age, past smoking, hypertension and high cholesterol level were observed particularly in males, while the association of long sleep duration with CHD was only observed in females. Hypertension was associated with CHD for both genders. CONCLUSIONS: Gender, age, past smoking, long sleep duration, hypertension and high cholesterol level were significantly associated with CHD among T2D patients; however, such associations differed by gender. Such gender disparities should be considered in the prevention and treatment of T2D.

Gender Differences in HIV Sexual Risk Behaviors Among Clients of Substance Use Disorder Treatment Programs in the U.S.

This study examined differences in sexual risk behaviors by gender and over time among 1281 patients (777 males and 504 females) from 12 community-based substance use disorder treatment programs throughout the United States participating in CTN-0032, a randomized control trial conducted within the National Drug Abuse Treatment Clinical Trials Network. Zero-inflated negative binomial and negative binomial models were used in the statistical analysis. Results indicated significant reductions in most types of sexual risk behaviors among substance users regardless of the intervention arms. There were also significant gender differences in sexual risk behaviors. Men (compared with women) reported more condomless sex acts with their non-primary partners (IRR = 1.80, 95 % CI 1.21-2.69) and condomless anal sex acts (IRR = 1.74, 95 % CI 1.11-2.72), but fewer condomless sex partners (IRR = 0.87, 95 % CI 0.77-0.99), condomless vaginal sex acts (IRR = 0.83, 95 % CI 0.69-1.00), and condomless sex acts within 2 h of using drugs or alcohol (IRR = 0.70, 95 % CI 0.53-0.90). Gender-specific intervention approaches are called for in substance use disorder treatment.

Bayesian Cox Proportional Hazards Model in Survival Analysis of HACE1 Gene with Age at Onset of Alzheimer's Disease.

Alzheimer's disease (AD), the most common form of dementia, is a chronic neurodegenerative disease. The HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1) gene is expressed in human brain and may play a role in the pathogenesis of neurodegenerative disorders. Till now, no previous study has reported the association of the HACE1 gene with the risk and age at onset (AAO) of AD; while few studies have checked the proportional hazards assumption in the survival analysis of AAO of AD using Cox proportional hazards model. In this study, we examined the associations of 14 single nucleotide polymorphisms (SNPs) in the HACE1 gene with the risk and the AAO of AD using 791 AD patients and 782 controls. Multiple logistic regression model identified one SNP (rs9499937 with p = 1.8×10-3) to be associated with the risk of AD. For survival analysis of AAO, both classic Cox regression model and Bayesian survival analysis using the Cox proportional hazards model were applied to examine the association of each SNP with the AAO. The hazards ratio (HR) with its 95% confidence interval (CI) was estimated. Survival analysis using the classic Cox regression model showed that 4 SNPs were significantly associated with the AAO (top SNP rs9499937 with HR=1.33, 95%CI=1.13-1.57, p=5.0×10-4). Bayesian Cox regression model showed similar but a slightly stronger associations (top SNP rs9499937 with HR=1.34, 95%CI=1.11-1.55) compared with the classic Cox regression model. Using an independent family-based sample, one SNP rs9486018 was associated with the risk of AD (p=0.0323) and the T-T-G haplotype from rs9786015, rs9486018 and rs4079063 showed associations with both the risk and AAO of AD (p=2.27×10-3 and 0.0487, respectively). The findings of this study provide first evidence that several genetic variants in the HACE1 gene were associated with the risk and AAO of AD.

Polymorphisms in PDLIM5 gene are associated with alcohol dependence, type 2 diabetes, and hypertension.

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in alcohol dependence (AD), bipolar disorder, and major depressive disorder; however, no study has identified shared genetic variants within PDLIM5 gene among AD, type 2 diabetes (T2D), and hypertension. This study investigated the association of 72 single nucleotide polymorphism (SNPs) with AD (1066 AD cases and 1278 controls) in the Study of Addiction - Genetics and Environment (SAGE) sample and 47 SNPs with T2D (878 cases and 2686 non-diabetic) and hypertension (825 cases and 2739 non-hypertensive) in the Marshfield sample. Multiple logistic regression models in PLINK software were used to examine the associations of genetic variants with AD, T2D, and hypertension and SNP x alcohol consumption interactions for T2D and hypertension. Twenty-five SNPs were associated with AD in the SAGE sample (p < 0.05); rs1048627 showed the strongest association with AD (p = 5.53 × 10-4). Of the 25 SNPs, 5 SNPs showed associations with both AD in the SAGE sample and T2D in the Marshfield sample (top SNP rs11097432 with p = 0.00107 for T2D and p = 0.0483 for AD) while 6 SNPs showed associations with both AD in the SAGE sample and hypertension in the Marshfield sample (top SNP rs12500426 with p = 0.0119 for hypertension and p = 1.51 × 10-3 for AD). SNP (rs6532496) showed significant interaction with alcohol consumption for hypertension. Our results showed that several genetic variants in PDLIM5 gene influence AD, T2D and hypertension. These findings offer the potential for new insights into the pathogenesis of AD, T2D, and hypertension.

Non-parametric Survival Analysis of EPG5 Gene with Age at Onset of Alzheimer's Disease.

Non-parametric methods such as Wilcoxon test have the advantages of no assumptions for the underlying survival distributions. Alzheimer's disease (AD) is a chronic neurodegenerative disease while the ectopic P-granules autophagy protein 5 homolog (EPG5 gene) is highly expressed in human brain and may implicate in the pathogenesis of neurodegenerative disorders. The present study explored the associations of 26 single-nucleotide polymorphisms (SNPs) in the EPG5 gene with the age at onset (AAO) of AD using a family-based association test (FBAT)-Wilcoxon statistic in a family-based study. Then a replication study using a case-control sample was conducted to perform Wilcoxon test in Kaplan-Meier survival analysis of AAO. The results from FBAT-generalized estimating equations (FBAT-GEE) statistics and FBAT-Wilcoxon test showed that seven SNPs (top SNP rs495078 with p = 1.29 × 10-3) were significantly associated with the risk of AD, and eight SNPs (top SNP rs11082498 with p = 3.55 × 10-4) were associated with the AAO of AD in the family-based study (p < 0.05). In the replicated data, three SNPs were associated with AAO by using the Wilcoxon test, where the mean AAO was approximately 2.2 years earlier in individuals who had at least one minor allele of the top AAO-associated SNP rs9963463 (p = 0.0018) compared with those who were homozygous for the major allele. These findings from non-parametric survival analyses provide evidence for several genetic variants in EPG5 influencing the AAO of AD and will serve as a resource for replication in other populations.

Bayesian logistic regression in detection of gene-steroid interaction for cancer at PDLIM5 locus.

The PDZ and LIM domain 5 (PDLIM5) gene may play a role in cancer, bipolar disorder, major depression, alcohol dependence and schizophrenia; however, little is known about the interaction effect of steroid and PDLIM5 gene on cancer. This study examined 47 single-nucleotide polymorphisms (SNPs) within the PDLIM5 gene in the Marshfield sample with 716 cancer patients (any diagnosed cancer, excluding minor skin cancer) and 2848 noncancer controls. Multiple logistic regression model in PLINK software was used to examine the association of each SNP with cancer. Bayesian logistic regression in PROC GENMOD in SAS statistical software, ver. 9.4 was used to detect gene- steroid interactions influencing cancer. Single marker analysis using PLINK identified 12 SNPs associated with cancer (P< 0.05); especially, SNP rs6532496 revealed the strongest association with cancer (P = 6.84 × 10⁻³); while the next best signal was rs951613 (P = 7.46 × 10⁻³). Classic logistic regression in PROC GENMOD showed that both rs6532496 and rs951613 revealed strong gene-steroid interaction effects (OR=2.18, 95% CI=1.31-3.63 with P = 2.9 × 10⁻³ for rs6532496 and OR=2.07, 95% CI=1.24-3.45 with P = 5.43 × 10⁻³ for rs951613, respectively). Results from Bayesian logistic regression showed stronger interaction effects (OR=2.26, 95% CI=1.2-3.38 for rs6532496 and OR=2.14, 95% CI=1.14-3.2 for rs951613, respectively). All the 12 SNPs associated with cancer revealed significant gene-steroid interaction effects (P < 0.05); whereas 13 SNPs showed gene-steroid interaction effects without main effect on cancer. SNP rs4634230 revealed the strongest gene-steroid interaction effect (OR=2.49, 95% CI=1.5-4.13 with P = 4.0 × 10⁻4 based on the classic logistic regression and OR=2.59, 95% CI=1.4-3.97 from Bayesian logistic regression; respectively). This study provides evidence of common genetic variants within the PDLIM5 gene and interactions between PLDIM5 gene polymorphisms and steroid use influencing cancer.

Long noncoding RNAs in psychiatric disorders.

Long noncoding RNAs (lncRNAs) are nonprotein coding transcripts longer than 200 nucleotides. Many of these lncRNAs have regulatory functions and have recently emerged as major players in governing fundamental biological processes. Here, we review the definition, distribution, identification, databases, analysis, classification, and functions of lncRNAs. We also discuss the potential roles of lncRNAs in the etiological processes of psychiatric disorders and the implications for clinical diagnosis and treatment.

Genetic variants in the CPNE5 gene are associated with alcohol dependence and obesity in Caucasian populations.

Alcohol addiction may increase the risk of obesity due to shared genetic components. The Copine V (CPNE5) gene is involved in Ca(2+) binding and may play an important role in the development of the central nervous system. This study tested the genetic associations of 77 single-nucleotide polymorphisms (SNPs) within the CPNE5 gene with alcohol dependence (AD) and obesity using a Caucasian sample - The Study of Addiction - Genetics and Environment (SAGE) sample (1066 AD cases and 1278 non-AD controls, 422 obese cases and 1395 non-obese controls). The Marshfield sample (1442 obese cases and 2122 non-obese controls) was used for replication of obesity. Multiple logistic regression analysis was performed using the PLINK software. In the SAGE sample, we identified 10 SNPs associated with AD and 17 SNPs associated with obesity (p < 0.05). Interestingly, 6 SNPs (rs9986517, rs9470387, rs3213534, rs10456444, rs3752482, and rs9470386) were associated with both AD (OR = 0.77, 0.77, 0.83, 0.84, 0.79 and 1.14, respectively; p = 9.72 × 10(-5), 1.1 × 10(-4), 4.09 × 10(-3), 5.26 × 10(-3), 1.59 × 10(-2), and 3.81 × 10(-2), respectively) and obesity (OR = 0.77, 0.77, 0.78, 0.77, 0.68 and 1.18, respectively; p = 2.74 × 10(-3), 2.69 × 10(-3), 2.45 × 10(-3), 1.01 × 10(-3), 5.18 × 10(-3) and 3.85 × 10(-2), respectively). In the Marshfield sample, rs3752480 was associated with obesity (p = 0.0379). In addition, four SNPs (rs9986517, rs10456444, rs7763347 and rs4714010) showed associations with obesity in the meta-analysis using both samples (p = 0.00493, 0.0274, 0.00346, and 0.0141, respectively). These findings provide the first evidence of common genetic variants in the CPNE5 gene influencing both the AD and obesity; and will serve as a resource for replication in other populations.

Alcohol Consumption, Depression, Insomnia and Colorectal Cancer Screening: Racial Differences.

BACKGROUND: Mortality from colorectal cancer (CRC) can be reduced drastically by early detection and early treatment. However, uptake of CRC screening is relatively low, about 50% for those whom the test is highly recommended. OBJECTIVES: We examined the influence of and racial differences in depression, insomnia, alcohol use, and tobacco use on CRC screening uptake in the US. PATIENTS AND METHODS: Analysis of the 2012 National Health Information Survey data was conducted. Both weighted univariate and multiple logistic regression analyses were performed in SAS to estimate the odds ratios (ORs) and their 95% confidence intervals (CIs). A total of 21511 participants were included in the analysis. RESULTS: Prevalence of CRC screening in the participants was 19%. Adjusting for all factors, insomnia (OR = 1.18, 95%CI = 1.06 - 1.32), moderate alcohol drinking (OR = 1.16, 95%CI = 1.01 - 1.30), past smoking (OR = 1.17, 95%CI = 1.04 - 1.32), depression (OR = 1.37, 95%CI = 1.18 - 1.58), African American (AA) race, and cancer history were positively associated with CRC screening. Females and Single were inversely associated with CRC screening prevalence. In stratified analysis by races (White and AA), depression was associated with CRC screening in both races. Marital status, smoking, cancer history and insomnia were associated with CRC screening in Whites only; while alcohol use was associated with CRC screening in AAs only. CONCLUSIONS: We have found significant associations between lifestyle factors (alcohol consumption and smoking) and mental health problems (depression and insomnia) and CRC screening uptake. To improve overall CRC screening uptake in the US, it is important to consider racial differences in predictors and tailor appropriate interventions to each racial/ethnic group.

Age Differences in the Trends of Smoking Among California Adults: Results from the California Health Interview Survey 2001-2012.

The aim is to study the trends of cigarette smoking from 2001 to 2012 using a California representative sample in the US. Data was taken from the California Health Interview Survey (CHIS) from 2001 to 2012, which is a population-based, biennial, random digit-dial telephone survey of the non-institutionalized population. The CHIS is the largest telephone survey in California and the largest state health survey in the US. 282,931 adults (n = 184,454 with age 18-60 and n = 98,477 with age >60) were included in the analysis. Data were weighted to be representative and adjusted for potential covariance and non-response biases. During 2001-2012, the prevalence of current smoking decreased from 18.86 to 15.4 % among adults age 18-60 (ß = -0.8, p = 0.0041). As for adults age >60, the prevalence of current smoking trend decreased with variations, started from 9.66 % in 2001, slightly increased to 9.74 % in 2003, but then gradually decreased, falling to 8.18 % in 2012. In 2012, there was a 14 % reduction of daily smoking adults age 18-60 (OR 0.84, 95 % CI 0.76-0.93, p = 0.0006) compared to 2001, while no significant reduction of daily smoking was observed for those age >60. The reductions of smoking prevalence for adults younger than 60 are encouraging. However, there is a concern for smoking cessation rates among those older than 60 years of age, particularly for African Americans.

Polymorphisms within ASTN2 gene are associated with age at onset of Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurological condition associated with genetic profiles that are still not completely understood. We performed a family-based low-density genome-wide association analysis of age at onset (AAO) in AD (244 patients and their relatives) using Illumina 6 K single-nucleotide polymorphisms (SNPs) panel and the FBAT-logrank statistic. We observed 10 SNPs associated with AAO in AD with p < 2 × 10(-3). The most significant hit within a known gene, the neuronal protein astrotactin 2 (ASTN2), was SNP rs1334071 (p = 8.74 × 10(-4)). ASTN2 has been implicated in several neuropsychiatric disorders, including cognitive disorders, autism and schizophrenia. We then conducted a replication study focusing on ASTN2 gene in a Canadian sample of 791 AD patients and 782 controls using the logrank test. Five ASTN2 SNPs (highest association is rs16933774 with p = 0.0053) showed associations with AAO in this Canadian sample (p < 0.05). Furthermore, Kaplan-Meier survival analysis of SNP rs16933774 showed that the AAO of AD in individuals heterozygous for AG genotype of rs16933774 (median of AAO = 68.5 years) was approximately 4.5 years earlier than those individuals having the AA genotype (median of AAO = 73 years). In conclusion, a significant association of ASTN2 genetic variants with AAO of AD in two independent samples demonstrates a role for ASTN2 in the pathogenesis of AD. Future functional studies of this gene may help to characterize the genetic architecture of the AAO of AD. Genetic factors in AAO may be a critical factor for early AD intervention and prevention efforts.