Family-based Cohort Study Research Articles

PFAS Exposure Levels in a Family-based Cohort Study in Minnesota

PFAS Exposure Levels in a Family-based Cohort Study in Minnesota

Healthy Lifestyles Modify the Association of Melatonin Receptor 1B Gene and Ischemic Stroke: A Family-Based Cohort Study in Northern China.

Limited research has reported the association between MTNR1B gene polymorphisms and ischemic stroke (IS), and there is insufficient evidence on whether adopting a healthy lifestyle can mitigate genetic risks in this context. This study aimed to investigate the associations between MTNR1B gene variants (rs10830963 and rs1387153) and IS, examining the potential effect of gene-lifestyle interactions on IS risk. Conducted in northern China, this family-based cohort study involved 5116 initially IS-free subjects. Genotype data for rs10830963 and rs1387153 in MTNR1B were collected. Eight modifiable lifestyle factors, including body mass index (BMI), smoking, alcohol consumption, dietary habits, physical activity, sedentary time, sleep duration, and chronotype, were considered in calculating healthy lifestyle scores. Multilevel Cox models were used to examine the associations between MTNR1B variants and IS. Participants carrying the rs10830963-G and rs1387153-T alleles exhibited an elevated IS risk. Each additional rs10830963-G allele and rs1387153-T allele increased the IS risk by 36% (HR = 1.36, 95%CI, 1.12-1.65) and 32% (HR = 1.32, 95%CI, 1.09-1.60), respectively. Participants were stratified into low, medium, and high healthy lifestyle score groups (1537, 2188, and 1391 participants, respectively). Genetic-lifestyle interactions were observed for rs10830963 and rs1387153 (p for interaction < 0.001). Notably, as the healthy lifestyle score increased, the effect of MTNR1B gene variants on IS risk diminished (p for trend < 0.001). This study underscores the association between the MTNR1B gene and IS, emphasizing that adherence to a healthy lifestyle can mitigate the genetic predisposition to IS.

Generation Scotland: an update on Scotland’s longitudinal family health study

PurposeGeneration Scotland (GS) is a large family-based cohort study established as a longitudinal resource for research into the genetic, lifestyle and environmental determinants of physical and mental health. It comprises...

The Tehran longitudinal family-based cardiometabolic cohort study sheds new light on dyslipidemia transmission patterns

Dyslipidemia, as a metabolic risk factor, with the strongest and most heritable independent cause of cardiovascular diseases worldwide. We investigated the familial transmission patterns of dyslipidemia through a longitudinal family-based cohort, the Tehran Cardiometabolic Genetic Study (TCGS) in Iran. We enrolled 18,729 individuals (45% were males) aged > 18 years (mean: 38.15 (15.82)) and observed them over five 3-year follow-up periods. We evaluated the serum concentrations of total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol with the first measurement among longitudinal measures and the average measurements (AM) of the five periods. Heritability analysis was conducted using a mixed-effect framework with likelihood-based and Bayesian approaches. The periodic prevalence and heritability of dyslipidemia were estimated to be 65.7 and 42%, respectively. The likelihood of an individual having at least one dyslipidemic parent reveals an OR = 6.94 (CI 5.28–9.30) compared to those who do not have dyslipidemic parents. The most considerable intraclass correlation of family members was for the same-sex siblings, with ICC ~ 25.5%. For serum concentrations, heritability ranged from 33.64 to 60.95%. Taken together, these findings demonstrate that familial transmission of dyslipidemia in the Tehran population is strong, especially within the same-gender siblings. According to previous reports, the heritability of dyslipidemia in this population is considerably higher than the global average.

A co-designed, community-based intensive health behavior intervention promotes participation and engagement in youth with risk factors for type 2 diabetes.

Obesity among youth (children and adolescents) is associated with increased risk for youth-onset type 2 diabetes. Lifestyle change can delay or prevent the development of type 2 diabetes, yet real-world implementation of health behavior recommendations is challenging. We previously engaged youth with risk factors for type 2 diabetes, their caregivers, and professionals in a human-centered design study to co-design a lifestyle change program. Here we report the outcomes for this 16-week co-designed lifestyle change program for youth at risk for T2D and their caregivers. This single-arm family-based cohort study included youth aged 7-18 years, with BMI ≥85th percentile (overweight or obese) and at least one additional risk factor for type 2 diabetes, and their caregivers. Clinical (BMI, HbA1c), self-reported physical activity, and quality of life outcomes were evaluated at baseline (B), post-intervention (M4), and 1 year (M12) following the intervention. Seventy-eight youth (mean age 12.4 ± 2.7y, 67% female, 37.8% white) and 65 caregivers were included in the data analysis. Youth baseline BMI z-scores (2.26 ± 0.47) and HbA1c (5.3 ± 0.3) were unchanged at follow up time points [BMI z-scores M4 (2.25 ± 0.52), M12 (2.16 ± 0.58), p-value 0.46], [HbA1c M4 (5.3 ± 0.3), M12 (5.2 ± 0.3), p-value (0.04)]. Youth reported increased physical activity at M4 (p = 0.004), but not at M12. Youth quality of life scores increased at M12 (p=0.01). Families who attended at least one session (n=41) attended an average of 9 out of 16 sessions, and 37 percent of families attended 13 or more sessions. A co-designed, community-based lifestyle intervention promotes increased physical activity, improved quality of life, maintenance of BMI z-scores and HbA1c, and engagement in youth with risk factors for T2D.

Familial Correlation and Heritability of Hand Grip Strength in Korean Adults (Korea National Health and Nutrition Examination Survey 2014 to 2019).

The onset and progression of sarcopenia are highly variable among individuals owing to genetic and environmental factors. However, there are a limited number of studies measuring the heritability of muscle strength in large numbers of parent-adult offspring pairs. We aimed to investigate the familial correlation and heritability of hand grip strength (HGS) among Korean adults. This family-based cohort study on data from the Korea National Health and Nutrition Examination Survey (2014 to 2019) included 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations of HGS were calculated in different pairs of relatives. Variance component methods were used to estimate heritability. The heritability estimate of HGS among Korean adults was 0.154 (standard error, 0.066). Correlation coefficient estimates for HGS between parent-offspring, sibling, and spouse pairs were significant at 0.07, 0.10, and 0.23 (P<0.001, P=0.041, and P<0.001, respectively). The total variance in the HGS phenotype was explained by additive genetic (15.4%), shared environmental (11.0%), and unique environmental (73.6%) influences. The odds of weak HGS significantly increased in the offspring of parents with weak HGS (odds ratio [OR], 1.69-3.10; P=0.027-0.038), especially in daughters (OR, 2.04-4.64; P=0.029-0.034). HGS exhibits a familial correlation and significant heritable tendency in Korean adults. Therefore, Asian adults, especially women, who have parents with weak HGS, need to pay special attention to their muscle health with the help of healthy environmental stimuli.

Association between cumulative psychosocial adversity in the family and ADHD and autism: a family-based cohort study

Cumulative exposure to psychosocial adversity at an early age has been shown to be a risk factor for attention-deficit hyperactivity disorder (ADHD) and autism that often co-occur. However, it is not clear if this association reflects a causal effect or familial confounding. We aimed to assess whether cumulative psychosocial adversity in the family increases the risk for ADHD and autism in offspring while accounting for unmeasured familial confounding. We used a population-based cohort of 1,877,901 individuals born in Sweden between 1990 and 2009. Participants were followed from the age of 3 until 2013, with a median follow up time of 13.8 years. We created a cumulative index based on 7 psychosocial adversity factors. We used Cox regression to estimate the hazard ratios (HRs) relating neurodevelopmental conditions to cumulative psychosocial adversity. To address familial confounding, the analyses were repeated in groups of relatives of different kinship: siblings and half-siblings and cousins. A dose-response relationship was observed between cumulative exposure to psychosocial adversity and ADHD at a general population level (covariate adjusted HRs (aHRs) with 95% confidence intervals ranged from 1.55 [one adversity; 1.53–1.58] to 2.65 [ ≥ 4 adversities; 1.98–3.54]). No clear dose-response relation was seen for autism (aHRs ranged from 1.04 [.59–1.84] to 1.37 [1.30–1.45]). HRs of ADHD and autism decreased with increasing level of kinship in the analysis of relatives. Cumulative exposure to psychosocial adversity was associated with both ADHD and autism in the general population, these associations were partly explained by unmeasured familial confounding between relatives. This highlights the need for using family-based designs in studies of psychosocial adversity and ADHD and autism.

KCNQ1 rs2237892 polymorphism modify the association between short-term ambient particulate matter exposure and fasting blood glucose: A family-based study

BackgroundThe association between particulate matter and fasting blood glucose (FBG) has shown conflicting results. Genome-wide association studies have shown that KCNQ1 rs2237892 polymorphism is associated with the risk of diabetes. Whether KCNQ1 rs2237892 polymorphism might modify the association between particulate matter and FBG is still uncertain. MethodsData collected from a family-based cohort study in Northern China, were used to perform the analysis. A generalized additive Gaussian model was used to examine the short-term effects of air pollutants on FBG. We further conducted interaction analyses by including a cross-product term of air pollutants by rs2237892 within KCNQ1 gene. ResultsA total of 4418 participants were included in the study. In the single pollutant model, the FBG level increased 0.0031 mmol/L with per 10 μg/m3 elevation in fine particular matter (PM2.5) for lag 0 day. After additional adjustments for nitrogen dioxide (NO2) and sulfur dioxide (SO2), similar results were observed for lag 0–2 days. As for particulate matter with particle size below 10 μm (PM10), the significant association between the daily average concentration of the pollutant and FBG level was observed for lag 0–3 days. Additionally, rs2237892 in KCNQ1 gene modified the association between PM and FBG level. The higher risk of FBG levels associated with elevations in PM10 and PM2.5 were more evident as the number of risk allele C increased. Individuals with a CC genotype had the highest risk of elevation in FBG levels. ConclusionShort-term exposures to PM2.5 and PM10 were associated with higher FBG levels. Additionally, rs2237892 in KCNQ1 gene might modify the association between the air pollutants and FBG levels.

ODP089 Familial correlation and heritability of muscle strength in Korean adults (KNHANES 2014-2019)

Abstract Objective The onset and progression of sarcopenia are highly variable between individuals due to genetic and environmental factors. However, studies that have measured muscle strength directly in large numbers of matched parent-adult offspring pairs are limited. In this study, we investigated familial correlation and heritability of handgrip strength (HGS) in Korean adults. Methods This was a family-based cohort study from the Korea National Health and Nutrition Examination Survey (2014-2019) including 5,004 Koreans aged ≥19 years from 1,527 families. HGS was measured using a digital grip strength dynamometer. Familial correlations for HGS were calculated in different types of relative pairs. Variance component methods were used to obtain heritability estimates. Results Mean HGS of parents were 39.3 ± 7.5 kg in fathers and 24.4 ± 5. 0 kg in mothers and those of offspring were 41.8 ± 8. 0 kg in sons and 24. 0 ± 4.8 kg in daughters. Correlation coefficient estimates between parent-offspring pairs, sibling pairs, and spouse pairs for HGS were significant as 0. 07, 0.10, and 0.23 (p &amp;lt;0. 001, p = 0. 041, and p &amp;lt;0. 001), respectively. The total variance of the phenotype under study was explained by additive genetic (15.4%), common shared environmental (11. 0%), and unique environmental (73.6%) influences. The risk of low HGS conferred by parents’ low HGS were found to be significant for individuals whose parents had low HGS (OR 3.10, 95%CI 1.14-8.45). Conclusion Muscle strength showed a familial correlation in Korean adults. A significant heritable tendency of muscle strength from parents to their adult offspring and common shared environmental influence can explain this correlation. Presentation: No date and time listed

Type 2 Diabetes Risk and Lipid Metabolism Related to the Pleiotropic Effects of an ABCB1 Variant: A Chinese Family-Based Cohort Study.

The single nucleotide polymorphism (SNP) rs4148727 in ABCB1 (encoding p-glycoprotein) is associated with lipid levels; however, its association with type 2 diabetes (T2DM) and its the genetic correlation with lipid profiles and T2DM are unclear. We included 2300 participants from 593 families. A generalized estimating equations (GEE) model and Cox regression models were used to estimate the SNP’s effects on T2DM and lipid profiles. The participation of the SNP in T2DM pathogenesis through lipid-associated pathways was tested using mediation analysis. The G allele of the SNP was related to a 32% (6–64%, p = 0.015) increase in T2DM risk. It was also associated with a 10% (1–20%, p = 0.029), 17% (3–32%, p = 0.015), and 4% (1–7%, p = 0.015) increment in total cholesterol (TC), triglyceride (TG), and apolipoprotein A (Apo-A) concentrations, respectively. According to the mediation analysis, only TG (6.9%) and Apo-B (4.0%) had slight but significant mediation effects on the total impact of the SNP on T2DM. The pleiotropic effects of the ABCB1 variant on T2DM and lipids likely act via different pathways. The biological mechanisms should be verified in a future study.

Associations of prenatal exposure to perfluoroalkyl substances with preterm birth: A family-based birth cohort study

Studies have investigated associations between maternal exposure to PFAS and preterm birth, but the impact of paternal and overall family exposure to PFAS mixtures on preterm birth remains unknown. To address this knowledge gap, a total of 355 preterm births and 481 controls were selected for a family-based birth cohort study in a coastal area of China, between 2016 and 2018. Seven PFAS, including perfluorobutanoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA) and perfluorodecanoic acid (PFDA), were quantified in maternal, paternal and neonatal sera. Preterm birth was defined as live delivery at <37 completed gestational weeks. Bayesian kernel machine regression (BKMR) model was used to inspect the combined effect of family PFAS mixtures. Latent class analysis was used to identify family-level PFAS exposure profiles. Multiple linear regression analysis showed higher odds of preterm birth in association with higher maternal PFBA (OR = 1.16, 95%CI:1.09, 1.25), PFOA (OR = 1.51, 95%CI:1.27, 1.80), PFOS (OR = 2.07, 95%CI:1.70, 2.52) and PFNA (OR = 1.36, 95%CI: 1.01, 1.83), and neonatal PFBA (OR = 1.16, 95%CI:1.05,1.29), PFHxA (OR = 1.46, 95%CI:1.32, 1.62), PFHxS (OR = 1.15, 95%CI:1.05, 1.26) and PFNA (OR = 1.30, 95%CI:1.09,1.56). The associations were reversed between individual paternal PFAS exposures and preterm birth. At the family level, higher PFAS mixture concentration was associated with higher odds of preterm birth. In particular, higher PFNA and PFDA exposure was associated with greater preterm birth risk (OR = 2.55, 95%CI:1.45, 4.50). The PFAS-preterm association was modified by family-level seafood consumption. Our results suggest that higher family-level PFNA and PFDA exposure was associated with greater preterm birth risk, although the results for individual paternal, maternal and neonatal PFAS exposures were contradictory. If replicated in other coastal areas, these findings highlight a need to focus on the family triad and to consider seafood consumption when assessing the reproductive toxicity of PFAS exposure.

Sex, age, and ethnic dependency of lipoprotein variants as the risk factors of ischemic heart disease: a detailed study on the different age-classes and genders in Tehran Cardiometabolic Genetic Study (TCGS)

Biological processes involving environmental and genetic factors drive the interplay between age- and sex-regulating lipid profile. The relation between variations in the LPA gene with increasing the risk of coronary heart disease is dependent on population differences, sex, and age. The present study tried to do a gene candidate association analysis in people with myocardial infarction (MI) in a 22 year cohort family-based longitudinal cohort study, Tehran Cardiometabolic Genetic Study (TCGS). After adjusting p value by the FDR method, only the association of rs6415084 with the MI probability and the age-of-CHD-onset was significant in males in their middle age (p < 0.005). Surprisingly, a lack of association was observed for the rest of the markers (16 SNPs). These results revealed the moderator effects of age and sex on the association between the genetic variants (SNPs) of LPA and heart disease risk. Our observations may provide new insights into the biology that underlies lipid profile with age or the sexual dimorphism of Lp(a) metabolism. Finally, Lp(a) appears to be an independent risk factor; however, the role of sex and ethnicity is important.

An atlas of metallome and metabolome interactions and associations with incident diabetes in the Strong Heart Family Study.

Chronic exposure to certain metals plays a role in disease development. Integrating untargeted metabolomics with urinary metallome data may contribute to better understanding the pathophysiology of diseases and complex molecular interactions related to environmental metal exposures. To discover novel associations between urinary metal biomarkers and metabolism networks, we conducted an integrative metallome-metabolome analysis using a panel of urinary metals and untargeted blood metabolomic data from the Strong Heart Family Study (SHFS). The SHFS is a prospective family-based cohort study comprised of American Indian men and women recruited in 2001-2003. This nested case-control analysis of 145 participants of which 50 developed incident diabetes at follow up in 2006-2009, included participants with urinary metal and untargeted metabolomic data. Concentrations of 8 creatinine-adjusted urine metals/metalloids [antimony (Sb), cadmium (Cd), lead (Pb), molybdenum (Mo), selenium (Se), tungsten (W), uranium (U) and zinc (Zn)], and 4 arsenic species [inorganic arsenic (iAs), monomethylarsonate (MMA), dimethylarsinate (DMA), and arsenobetaine (AsB)] were measured. Global metabolomics was performed on plasma samples using high-resolution Orbitrap mass spectrometry. We performed an integrative network analysis using xMWAS and a metabolic pathway analysis using Mummichog. 8,810 metabolic features and 12 metal species were included in the integrative network analysis. Most metal species were associated with distinct subsets of metabolites, forming single-metal-multiple-metabolite clusters (|r|>0.28, p-value<0.001). DMA (clustering with W), iAs (clustering with U), together with Mo and Se showed modest interactions through associations with common metabolites. Pathway enrichment analysis of associated metabolites (|r|>0.17, p-value<0.1) showed effects in amino acid metabolism (AsB, Sb, Se and U), fatty acid and lipid metabolism (iAs, Mo, W, Sb, Pb, Cd and Zn). In stratified analyses among participants who went on to develop diabetes, iAs and U clustered together through shared metabolites, and both were associated with the phosphatidylinositol phosphate metabolism pathway; metals were also associated with metabolites in energy metabolism (iAs, MMA, DMA, U, W) and xenobiotic degradation and metabolism (DMA, Pb) pathways. In this integrative analysis of multiple metals and untargeted metabolomics, results show common associations with fatty acid, energy and amino acid metabolism pathways. Results for individual metabolite associations differed for different metals, indicating that larger populations will be needed to confirm the metal-metal interactions detected here, such as the strong interaction of uranium and inorganic arsenic. Understanding the biochemical networks underlying metabolic homeostasis and their association with exposure to multiple metals may help identify novel biomarkers, pathways of disease, potential signatures of environmental metal exposure.

Prognostic value of different maternal obesity phenotypes in predicting offspring obesity in a family-based cohort study

BackgroundParental weight is studied as an important determinant of childhood obesity; however, obesity-related metabolic abnormalities have been less considered as determinants of childhood obesity. This study aimed to investigate the association between maternal obesity phenotypes and incidence of obesity in their offspring.MethodsThis longitudinal study was conducted within the framework of the Tehran Lipid and Glucose Study. A total of 2151 non-obese children who had complete parental information were followed for incidence of obesity over a mean of 148.7 ± 34.7 months. Obesity in children was defined using the World Health Organization criteria. Maternal body mass index (BMI) was classified into three categories: normal weight, overweight and obese. Dysmetabolic status was considered as having metabolic syndrome or diabetes. Metabolic syndrome and diabetes were defined according to the Joint Interim Statement and American diabetes association criteria, respectively. Considering maternal BMI categories and metabolic status, six obesity phenotypes were defined as followed: 1) normal weight and normal metabolic status, 2) overweight and normal metabolic status, 3) obese and normal metabolic status, 4) normal weight and dysmetabolic status, 5) overweight and dysmetabolic status, and 6) obese and dysmetabolic status. The association between maternal obesity phenotypes and incidence of obesity in children was studied using Cox proportional regression hazard model.ResultsIn male offspring, the risk of incidence of obesity significantly increased in those with maternal obesity phenotypes including overweight/normal metabolic: 1.75(95% CI: 1.10–2.79), obese/normal metabolic: 2.60(95%CI: 1.51–4.48), overweight/dysmetabolic: 2.34(95%CI: 1.35–4.03) and obese/dysmetabolic: 3.21(95%CI: 1.94–5.03) compared to the normal weight/normal metabolic phenotype. Similarly, in girls, the risk of incidence of obesity significantly increased in offspring with maternal obesity phenotypes including overweight/normal metabolic: 2.39(95%CI: 1.46–3.90), obese/normal metabolic: 3.55(95%CI: 1.94–6.46), overweight/dysmetabolic: 1.92(95%CI: 1.04–3.52) and obese/dysmetabolic: 3.89(95%CI: 2.28–6.64) compared to normal weight/normal metabolic phenotype. However, maternal normal weight/dysmetabolic phenotype did not significantly change the risk of obesity in both male and female offspring.ConclusionExcept for normal weight/dysmetabolic phenotype, all maternal obesity phenotypes had significant prognostic values for incidence of offspring obesity with the highest risk for obese/dysmetabolic phenotype. This study provides valuable findings for identifying the first line target groups for planning interventions to prevent childhood obesity.

Abstract A25: Collecting gut microbiome in the 10,000 Families Study

Abstract The 10,000 Families Study (10KFS) is a family-based prospective cohort study, the goal of which is to collect information about health-related outcomes, including cancer, in multigeneration families. Since 2017, we have been conducting a pilot feasibility study to prepare for the implementation of 10KFS. At baseline, eligible participants answer a questionnaire about demographics and lifestyle factors and attend a health fair during which trained staff measure their blood pressure, vision, hearing, and several other characteristics, as well as collect blood, urine, and saliva. Also, during the heath fair participants receive easy-to-use kits that enable them to collect stool samples in the convenience of their home. The method for stool collection to characterize gut microbiome in this study was chosen based on a small pilot of three methods: (1) Omnigene Gut (DNA Genotek), (2) iSWAB-Microbiome Collection Kit (Mawi Corporation), and (3) a homemade kit including a BD culture swab and vial with RNAlater preservative. The second method (iSWAB) was unanimously chosen by the volunteers as most acceptable due to the ease of stool collection. The acceptability and reduction of the participant’s burden are of primary importance in this study, since an adult participant often collects stool samples from one or more of their children. The quality of DNA assessed by spectrophotometry (based on 260/280 and 260/230 ratios) was similar for the iSWAB and the Omnigene kits (gold standard), and the quantity using the iSWAB kit was sufficient to characterize gut microbiome. Thus, in our study, stool samples are collected by participants using iSWAB kits and then returned by mail within four days of collection to the central laboratory biorepository at the University of Minnesota – Advanced Research and Diagnostic Laboratory, where they are immediately frozen and stored at -80°C. To date, stool samples from 62 participants aged 0 to over 90 years have been returned (out of 139 kits that were given to participants). This collection method meets the requirements necessary for stool collection in large population studies: (1) it is fast and easy for participants to use; (2) a preservative in the tube allows stool samples to be kept without freezing for up to 8 weeks while maintaining intact and viable bacteria; (3) samples use little space during shipment and storage; and (4) the method is cost efficient. Citation Format: Anna Prizment, Deanna Gabrielson, DeAnn Lazovich, Sharon Minnerath, Heather H. Nelson, Jenny N. Poynter, Cavan Reilly, Michelle Roesler, Logan G. Spector, Bharat Thyagarajan. Collecting gut microbiome in the 10,000 Families Study [abstract]. In: Proceedings of the AACR Special Conference on Modernizing Population Sciences in the Digital Age; 2019 Feb 19-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(9 Suppl):Abstract nr A25.

Prevalence, Awareness, Treatment, and Control of Hypertension and Its Associated Risk Factors: Results from Baseline Survey of SWADES Family Cohort Study.

Methods In this prospective family-based cohort study, 573 families were included with a total of 997 participants aged 30 years and above. Baseline interviews were conducted in participant's homes using a combination of self-structured and standardized questionnaire. Blood pressure and plasma glucose were assessed for each participant. Results The prevalence of hypertension was 43%. It was slightly higher in women than men (43.7% vs. 41.4%). The mean systolic blood pressure in the hypertensive population was 141.9 mmHg and mean diastolic blood pressure was 85.3 mmHg. In total, 78% (86.2% in women, 62.9% in men) of the participants were aware of their hypertension. Among those aware, 60.4% (63.5% in women, 52.6% in men) of the participants were on treatment, and hypertension was controlled in 75.1% (77.5% women, 68% in men) of the participants on treatment. The prevalence of hypertension was higher among persons with comorbidities (diabetes 64.5%, transient ischemic attack 54.7%, and heart disease 64.4%). Prevalence was lower among persons who did regular vigorous intensity exercise versus those who did moderate intensity exercise (32% vs. 45.7%) and among nonsmokers versus smokers (42.2% vs. 46.6%). Conclusion The prevalence of hypertension in Kerala is high. Although awareness is quite high, there is a need to improve the number of persons with hypertension taking treatment.

Association of parental substance use disorder with offspring cognition: a population family-based study.

To assess whether parental substance use disorder (SUD) is associated with lower cognitive ability in offspring, and whether the association is independent of shared genetic factors. A population family-based cohort study utilizing national Swedish registries. Linear regression with increased adjustment of covariates was performed in the full population. In addition, the mechanism of the association was investigated with children-of-sibling analyses using fixed-effects regression with three types of sibling parents with increasing genetic relatedness (half-siblings, full siblings and monozygotic twins). A total of 3 004 401 people born in Sweden between 1951 and 1998. The exposure variable was parental SUD, operationalized as having a parent with life-time SUD diagnosis or substance-related criminal conviction in the National Patient Register or Crime Register, respectively. Outcomes were cognitive test score at military conscription and final school grades when graduating from compulsory school. Covariates included in the analyses were sex, birth year, parental education, parental migration status and parental psychiatric comorbid diagnoses. In the full population, parental SUD was associated with decreased cognitive test stanine scores at conscription [4.56, 95% confidence interval (CI)=4.55-4.57] and lower Z-standardized school grades (-0.43, 95% CI=-0.43 to -0.42) compared to people with no parental SUD (cognitive test: 5.17, 95% CI=5.17-5.18; grades: 0.09, 95% CI=0.08-0.09). There was evidence of a dose-response relationship, in that having two parents with SUD (cognitive test: 4.17, 95% CI=4.15-4.20; grades: -0.83, 95% CI=-0.84 to -0.82) was associated with even lower cognitive ability than having one parent with SUD (cognitive test: 4.60, 95% CI=4.59-4.60; grades: -0.38, 95% CI=-0.39 to -0.380). In the children-of-siblings analyses when accounting for genetic relatedness, these negative associations were attenuated, suggestive of shared underlying genetic factors. There appear to be shared genetic factors between parental substance use disorder (SUD) and offspring cognitive function, suggesting that cognitive deficits may constitute a genetically transmitted risk factor in SUD.

The China Family-Based Birth Cohort: A Study of Both Assisted Reproductive Technology and Spontaneous Pregnancies

Background: More than 1·0% of all births in China are through Assisted reproductive technology (ART). Concern is mounting over the safety of ART and the health impacts of ART on maternal and fetal health. Well-designed longitudinal cohort aiming to address the concern is yet sparse. The China National Birth Cohort (CNBC) Study is a family-based and prospective birth cohort study consisting of both Assisted reproductive technology (ART) pregnancies and spontaneous pregnancies. Which was set to comprehensively describe the incidence of birth outcomes from ART and spontaneous-conceived pregnancies and to systematically evaluate the environmental and genetic factors that may influence the birth outcomes of these pregnancies. Methods: CNBC was launched at 22 centers (located in 15 cities of China) in November 2016, and aims to complete recruitment of 10,000 couples who plan to have invitro fertilization or intra-cytoplasmic sperm injection (IVF/ICSI) treatments and 10,000 couples who have spontaneous pregnancies. The cohort data is collected from the biological parents and the offspring from the ART centers and obstetrics departments, respectively. Findings: By December 2018, CNBC had recruited 10,954 ART families and 10,618 spontaneous conceived families. Questionnaires (demographic, occupational, behavioral, environmental, nutritional and psychosocial factors, etc.), clinical data (obstetric and pediatric examination, and laboratory tests, etc.), and biospecimens (blood, urine, cord blood, follicular fluid, sperm, and seminal plasma, etc.) were collected respectively before embryo transfer, at the 1st, 2nd and 3rd trimester during pregnancy, and approximately 42 days, 6 months, 12 months, and 36 months after birth. Interpretation: The CNBC provided comprehensive data and bio-specimen resources from ART-received pregnancy and spontaneous pregnancy family, which will help identify the risk factors for ART pregnancies, and to elucidate heterogeneity of maternal and child health consequences between ART- and spontaneous-conceived populations. The CNBC data will be available on line, and researchers can apply with formal proposals. Funding: China National Key Research & Development (RD The Key Project of National Natural Science Foundation of China; The Innovation Capability Development Project of Jiangsu Province. Declaration of Interest: The authors declare that they have no conflict of interest. Ethical Approval: This study was approved by the institutional review board of CNBC, and written informed consent was obtained from all subjects.

Identifying novel metal biomarkers and biochemical networks in the Strong Heart Family Study

PDS 71: Exposome, Johan Friso Foyer, Floor 1, August 27, 2019, 4:30 PM - 5:30 PM Background: Chronic exposure to certain toxic metals plays a role in disease development. Integrating untargeted metabolomics with urinary metallome data may contribute to better understanding the pathophysiology of diseases and complex molecular interactions related to environmental metal exposures. Using a previously measured panel of urinary metals and untargeted metabolomics data available in the Strong Heart Family Study (SHFS), we conducted an integrative metallome-metabolome analysis to discover novel associations between urinary metal biomarkers and metabolism networks. Methods: The SHFS is a prospective family-based cohort study comprised of American Indian men and women recruited in 2001-2003. In this cross-sectional analysis, we included participants without baseline diabetes and with available metabolomic and urinary metal data (n=145). Concentrations of creatinine-adjusted urine metals/metalloids (antimony [Sb], cadmium [Cd], lead [Pb], molybdenum [Mo], selenium [Se], tungsten [W], uranium [U] and zinc [Zn]), and arsenic species (iAs, MMA, DMA, AsB) were measured. Global metabolomics was performed on plasma samples using high-resolution Orbitrap mass spectrometry. We performed an integrative network analysis using the R package xMWAS and used the R package Mummichog for the metabolic pathway analysis. Results: In our integrative network analysis, most metal species were associated with distinct subsets of metabolites, forming single-metal-multiple-metabolite clusters (correlation efficiency: |ρ|>0.3). DMA (clustering with W), iAs (clustering with U), together with Mo and Se showed modest interactions through associations with common metabolites. Pathway enrichment analysis of associated metabolites (|ρ|>0.17, P< 0.05) showed effects in amino acid metabolism (AsB, Sb, Se and U), fatty acid and lipid metabolism (iAs, Mo, W, Sb, Pb, Cd and Zn) and redox metabolism (Cd and Se). Conclusion: This first proof-of-concept study shows the importance of metal-metabolite interactions. Understanding the biochemical networks underlying metabolic homeostasis and their association with exposure to metals may help identify novel biomarkers and pathways of disease and potential signatures of metal exposure.

AMISH EYE STUDY: Baseline Spectral Domain Optical Coherence Tomography Characteristics of Age-Related Macular Degeneration.

To describe spectral domain optical coherence tomography (SD-OCT) findings in an Amish cohort to assess SD-OCT markers for early age-related macular degeneration (AMD). The authors performed a family-based prospective cohort study of 1,146 elderly Amish subjects (age range 50-99 years) (2,292 eyes) who had a family history of at least 1 individual with AMD. All subjects underwent complete ophthalmic examinations, SD-OCT using both Cirrus and Spectralis (20 × 20° scan area) instruments, fundus autofluorescence, infrared imaging, and color fundus photography. Spectral domain optical coherence tomography characteristics were analyzed in subjects with AMD (with and without subretinal drusenoid deposits [SDDs]) and normal healthy cohorts. Participants' mean age was 65.2 years (SD ± 11). Color fundus photographic findings in 596 (53%) subjects (1,009 eyes) were consistent with AMD; the remaining 478 (43%) subjects showed no signs of AMD. The choroid was significantly thinner on OCT (242 ± 76 µm, P < 0.001) in those with AMD compared with those without (263 ± 63 µm). Subretinal drusenoid deposits were found in 143 eyes (7%); 11 of the 143 eyes (8%) had no other manifestations of AMD. Drusen volume (P < 0.001) and area of geographic atrophy (P < 0.001) were significantly greater, and choroid was significantly (P < 0.001) thinner in subjects with SDDs versus those without SDDs. The authors describe spectral domain optical coherence tomography characteristics in an elderly Amish population with and without AMD, including the frequency of SDD. Although relatively uncommon in this population, the authors confirmed that SDDs can be found in the absence of other features of AMD and that eyes with SDDs have thinner choroids.