Depression, Stressful Life Events, and the Impact of Variation in the Serotonin Transporter: Findings from the National Longitudinal Study of Adolescent to Adult Health (Add Health).

BACKGROUND: The low transcriptionally efficient short-allele of the 5HTTLPR serotonin transporter polymorphism has been implicated to moderate the relationship between the experience of stressful life events (SLEs) and depression. Despite numerous attempts at replicating this observation, results remain inconclusive. METHODS: We examined this relationship in young-adult Non-Hispanic white males and females between the ages of 22 and 26 (n = 4724) participating in the National Longitudinal Study of Adolescent to Adult Health (Add Health) with follow-up information every six years since 1995. RESULTS: Linear and logistic regression models, corrected for multiple testing, indicated that carriers of one or more of the S-alleles were more sensitive to stress than those with two L-alleles and at a higher risk for depression. This relationship behaved in a dose-response manner such that the risk for depression was greatest among those who reported experiencing higher numbers of SLEs. In post-hoc analyses we were not able to replicate an interaction effect for suicide ideation but did find suggestive evidence that the effects of SLEs and 5HTTLPR on suicide ideation differed for males and females. There were no effects of childhood maltreatment. DISCUSSION: Our results provide partial support for the original hypothesis that 5-HTTLPR genotype interacts with the experience of stressful life events in the etiology of depression during young adulthood. However, even with this large sample, and a carefully constructed a priori analysis plan, the results were still not definitive. For the purposes of replication, characterizing the 5HTTLPR in other large data sets with extensive environmental and depression measures is needed.

The reliability of in-home measures of height and weight in large cohort studies: Evidence from Add Health.

BACKGROUND: With the emergence of obesity as a global health issue an increasing number of major demographic surveys are collecting measured anthropometric data. Yet little is known about the characteristics and reliability of these data. OBJECTIVES: We evaluate the accuracy and reliability of anthropometric data collected in the home during Wave IV of the National Longitudinal Study of Adolescent to Adult Health (Add Health), compare our estimates to national standard, clinic-based estimates from the National Health and Nutrition Examination Survey (NHANES) and, using both sources, provide a detailed anthropometric description of young adults in the United States. METHODS: The reliability of Add Health in-home anthropometric measures was estimated from repeat examinations of a random subsample of study participants. A digit preference analysis evaluated the quality of anthropometric data recorded by field interviewers. The adjusted odds of obesity and central obesity in Add Health vs. NHANES were estimated with logistic regression. RESULTS: Short-term reliabilities of in-home measures of height, weight, waist and arm circumference-as well as derived body mass index (BMI, kg/m2)-were excellent. Prevalence of obesity (37% vs. 29%) and central obesity (47% vs. 38%) was higher in Add Health than in NHANES while socio-demographic patterns of obesity and central obesity were comparable in the two studies. CONCLUSIONS: Properly trained non-medical field interviewers can collect reliable anthropometric data in a nationwide, home visit study. This national cohort of young adults in the United States faces a high risk of early-onset chronic disease and premature mortality.

The National Longitudinal Study of Adolescent to Adult Health (Add Health) sibling pairs genome-wide data.

Here we provide a detailed description of the genome-wide information available on the National Longitudinal Study of Adolescent to Adult Health (Add Health) sibling pair subsample (Harris et al. in Twin Res Hum Genet 16:391-398, 2013). A total of 2,020 samples were genotyped (including duplicates) arising from 1946 Add Health individuals from the sibling pairs subsample. After various steps for quality control (QC) and quality assurance (QA), we have high quality genome-wide data available on 1,888 individuals. In this report, we first highlight the QC and QA steps that were taken to prune the data of poorly performing samples and genetic markers. We further estimate the pairwise biological relationships using genome-wide data and compare those estimates to the assumed relationships in Add Health. Additionally, using genome-wide data from known regional reference populations from Europe, West Africa, North and South America, Japan and China, we estimate the relative genetic ancestry of the respondents. Finally, rather than conducting a traditional cross-sectional genome-wide association study (GWAS) of body mass index (BMI), we opted to utilize the extensive publicly available genome-wide information to conduct a weighted GWAS of longitudinal BMI while accounting for both family and ethnic variation.

Blood spot-based measures of glucose homeostasis and diabetes prevalence in a nationally representative population of young US adults.

PURPOSE: We investigated understudied biomarker-based diabetes among young US adults, traditionally characterized by low cardiovascular disease risk. METHODS: We examined 15,701 participants aged 24 to 32 years at Wave IV of the National Longitudinal Study of Adolescent Health (Add Health, 2008). The study used innovative and relatively noninvasive methods to collect capillary whole blood via finger prick at in-home examinations in all 50 states. RESULTS: Assays of dried blood spots produced reliable and accurate values of HbA1c. Reliability was lower for fasting glucose and lowest for random glucose. Mean (SD) HbA1c was 5.6% (0.8%). More than a quarter (27.4%) had HbA1c-defined prediabetes. HbA1c was highest in the black, non-Hispanic race/ethnic group, inversely associated with education, and more common among the overweight/obese and physically inactive. The prevalence of diabetes defined by previous diagnosis or use of antidiabetic medication was 2.9%. Further incorporating HbA1c and glucose values, the prevalence increased to 6.8%, and among these participants, 38.9% had a previous diagnosis of diabetes (i.e., aware). Among those aware, 37.6% were treated and 64.0% were controlled (i.e., HbA1c < 7%). CONCLUSIONS: A contemporary cohort of young adults faces a historically high risk of diabetes but there is ample opportunity for early detection and intervention.

Simple sequence repeats in the national longitudinal study of adolescent health: an ethnically diverse resource for genetic analysis of health and behavior.

Simple sequence repeats (SSRs) are one of the earliest available forms of genetic variation available for analysis and have been utilized in studies of neurological, behavioral, and health phenotypes. Although findings from these studies have been suggestive, their interpretation has been complicated by a variety of factors including, among others, limited power due to small sample sizes. The current report details the availability, diversity, and allele and genotype frequencies of six commonly examined SSRs in the ethnically diverse, population-based National Longitudinal Study of Adolescent Health. A total of 106,743 genotypes were generated across 15,140 participants that included four microsatellites and two di-nucleotide repeats in three dopamine genes (DAT1, DRD4, DRD5), the serotonin transporter, and monoamine oxidase A. Allele and genotype frequencies showed a complex pattern and differed significantly between populations. For both di-nucleotide repeats we observed a greater allelic diversity than previously reported. The availability of these six SSRs in a large, ethnically diverse sample with extensive environmental measures assessed longitudinally offers a unique resource for researchers interested in health and behavior.

MAOA genotype, childhood maltreatment, and their interaction in the etiology of adult antisocial behaviors.

BACKGROUND: Maltreatment by an adult or caregiver during childhood is a prevalent and important predictor of antisocial behaviors in adulthood. A functional promoter polymorphism in the monoamine oxidase A (MAOA) gene has been implicated as a moderating factor in the relationship between childhood maltreatment and antisocial behaviors. Although there have been numerous attempts at replicating this observation, results remain inconclusive. METHODS: We examined this gene-environment interaction hypothesis in a sample of 3356 white and 960 black men (aged 24-34) participating in the National Longitudinal Study of Adolescent Health. RESULTS: Primary analysis indicated that childhood maltreatment was a significant risk factor for later behaviors that violate rules and the rights of others (p < .05), there were no main effects of MAOA genotype, and MAOA genotype was not a significant moderator of the relationship between maltreatment and antisocial behaviors in our white sample. Post hoc analyses identified a similar pattern of results among our black sample in which maltreatment was not a significant predictor of antisocial behavior. Post hoc analyses also revealed a main effect of MAOA genotype on having a disposition toward violence in both samples and for violent convictions among our black sample. None of these post hoc findings, however, survived correction for multiple testing (p > .05). Power analyses indicated that these results were not due to insufficient statistical power. CONCLUSIONS: We could not confirm the hypothesis that MAOA genotype moderates the relationship between childhood maltreatment and adult antisocial behaviors.

Social, behavioral, and genetic linkages from adolescence into adulthood.

The influence of genetic factors on health and behavior is conditioned by social, cultural, institutional, and physical environments in which individuals live, work, and play. We encourage studies supporting multilevel integrative approaches to understanding these contributions to health, and describe the Add Health study as an exemplar. Add Health is a large sample of US adolescents in grades 7 to 12 in 1994-1995 followed into adulthood with 4 in-home interviews and biomarker collections, including DNA. In addition to sampling multiple environments and measuring diverse social and health behavior, Add Health features a fully articulated behavioral genetic sample (3000 pairs) and ongoing genotyping of 12,000 archived samples. We illustrate approaches to understanding health through investigation of the interplay among biological, psychosocial, and physical, contextual, or cultural experiences.

A tale of two countries: rethinking sexual risk for HIV among young people in South Africa and the United States.

PURPOSE: To compare the sexual behaviors of young people in South Africa (SA) and the United States (US) with the aim to better understand the potential role of sexual behavior in HIV transmission in these two countries that have strikingly different HIV epidemics. METHODS: Nationally representative, population-based surveys of young people aged 18-24 years from SA (n = 7,548) and the US (n = 13,451) were used for the present study. RESULTS: The prevalence of HIV was 10.2% in SA and <1% in the US. Young women and men in the US reported an earlier age of first sex than those in SA (mean age of coital debut for women: US [16.5], SA [17.4]; for men: US [16.4], SA [16.7]). The median number of lifetime partners is higher in the US than in SA: women: US (4), SA (2); men: US (4), SA (3). The use of condom at last sex is reported to be lower in the US than in SA: women: US (36.1%), SA (45.4%); men: US (48%), SA (58%). On average, young women in SA report greater age differences with their sex partners than young women in the US. CONCLUSION: Young people in the US report riskier sexual behaviors than young people in SA, despite the much higher prevalence of HIV infection in SA. Factors above and beyond sexual behavior likely play a key role in the ongoing transmission of HIV in South African youth, and thus should be urgently uncovered to develop maximally effective prevention strategies.

Discordance in national estimates of hypertension among young adults.

BACKGROUND: In the United States, where coronary heart disease (CHD) is the leading cause of mortality, CHD risk assessment is a priority and accurate blood pressure (BP) measurement is essential. METHODS: Hypertension estimates in the National Longitudinal Study of Adolescent Health (Add Health), Wave IV (2008)-a nationally representative field study of 15,701 participants aged 24-32-was referenced against NHANES (2007-2008) participants of the same age. We examined discordances in hypertension, and estimated the accuracy and reliability of blood pressure in the Add Health study. RESULTS: Hypertension rates (BP: ≥ 140/90 mm Hg) were higher in Add Health compared with NHANES (19% vs. 4%), but self-reported history was similar (11% vs. 9%) among adults aged 24-32. Survey weights and adjustments for differences in participant characteristics, examination time, use of antihypertensive medications, and consumption of food/caffeine/cigarettes before blood pressure measurement had little effect on between-study differences in hypertension estimates. Among Add Health participants interviewed and examined twice (full and abbreviated interviews), blood pressure was similar, as was blood pressure at the in-home and in-clinic examinations conducted by NHANES III (1988-1994). In Add Health, there was minimal digit preference in blood pressure measurements; mean bias never exceeded 2 mm Hg; and reliability (estimated as intraclass correlation coefficients) was 0.81 and 0.68 for systolic and diastolic BPs, respectively. CONCLUSIONS: The proportion of young adults in NHANES reporting a history of hypertension was twice that with measured hypertension, whereas the reverse was found in Add Health. Between-survey differences were not explained by digit preference, low validity, or reliability of Add Health blood pressure data, or by salient differences in participant selection, measurement context, or interview content. The prevalence of hypertension among Add Health Wave IV participants suggests an unexpectedly high risk of cardiovascular disease among US young adults and warrants further scrutiny.