Ley A. Killeya-Jones

Genomic risk profiling: attitudes and use in personal and clinical care of primary care physicians who offer risk profiling.

ABSTRACTBACKGROUNDGenomic risk profiling involves the analysis of genetic variations linked through statistical associations to a range of disease states. There is considerable controversy as to how, and even whether, to incorporate these tests into routine medical care.OBJECTIVETo assess physician attitudes and uptake of genomic risk profiling among an ‘early adopter’ practice group.DESIGNWe surveyed members of MDVIP, a national group of primary care physicians (PCPs), currently offering genomic risk profiling as part of their practice.POPULATIONAll physicians in the MDVIP network (N = 356)RESULTSWe obtained a 44% response rate. One third of respondents had ordered a test for themselves and 42% for a patient. The odds of having ordered personal testing were 10.51-fold higher for those who felt well-informed about genomic risk testing (p < 0.0001). Of those who had not ordered a test for themselves, 60% expressed concerns for patients regarding discrimination by life and long-term/disability insurers, 61% about test cost, and 62% about clinical utility. The odds of ordering testing for their patients was 8.29-fold higher among respondents who had ordered testing for themselves (p < 0.0001). Of those who had ordered testing for patients, concerns about insurance coverage (p = 0.014) and uncertain clinical utility (p = 0.034) were associated with a lower relative frequency of intention to order testing again in the future.CONCLUSIONSOur findings demonstrate that respondent familiarity was a key predictor of physician ordering behavior and clinical utility was a primary concern for genomic risk profiling. Educational and interpretive support may enhance uptake of genomic risk profiling.

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.

Prevalence and co-occurrence of psychiatric symptom clusters in the U.S. adolescent population using DISC predictive scales.

ObjectiveTo estimate 12-month prevalence and co-occurrence of symptoms of specific mental problems among US adolescents (12–17 years) by age, sex and racial/ethnic subgroups.MethodData from the 2000 National Household Survey of Drug Abuse (NHSDA) adolescent sample are used to estimate prevalence and co-occurrence rates using the DISC predictive scales. Multiple logistic regressions were used to derive significant correlates of each domain of DPS-derived symptom cluster indicators of psychiatric problems and of severe comorbidity, with control of demographics and environmental factors.SettingThe National Household Survey on Drug Abuse (NHSDA), a national household probability sample, includes a nationally representative sample of 12–17 year-old adolescents (N = 19,430), through in-home surveys.ResultsThree out of five adolescents screened positive for at least one DPS symptom cluster with estimates for specific symptom cluster ranging over 9.7% (substance use disorder), 13.4% (affective), 36.3% (disruptive-behavior), and 40.1% (anxiety). Co-occurrence was high with almost one-third of any DPS symptom cluster reporting multiple positive screens of four or more clusters. Blacks and younger females were most likely to report mental health problems and co-occurrence.ConclusionMental health problems among U.S. youth may be far more common than previously believed, although these symptoms have not yet reached the point of clinical impairment. The data speak to important patterns of age, gender and racial/ethnic differences in mental health problems deserving of further study.

Early Adolescent Romantic Partner Status, Peer Standing, and Problem Behaviors.

This study examined associations among early adolescent romantic relationships, peer standing, problem behaviors, and gender as a moderator of these associations, in a sample of 320 seventh-grade students. Popular and controversial status youth were more likely to have a romantic partner, whereas neglected status youth were less likely to have a romantic partner. Similarly, youth perceived as conventional and unconventional leaders were also more likely to have a romantic partner than were non-leaders. Youth who had a romantic partner drank more alcohol and were more aggressive than were youth who did not have a romantic partner. Among those youth who had romantic partners, those who reported having more deviance-prone partners were themselves more likely to use alcohol and to be more aggressive, and those who engaged in deviant behavior with their partners used more alcohol. However, these associations varied somewhat by gender. These findings underscore the salience of early romantic partner relationships in the adjustment of early adolescents.

Early adolescents' social standing in peer groups: behavioral correlates of stability and change

Sociometric nominations, social cognitive maps, and self-report questionnaires were completed in consecutive years by 327 students (56% girls) followed longitudinally from grade 7 to grade 8 to examine the stability of social standing in peer groups and correlates of changes in social standing. Social preference, perceived popularity, network centrality, and leadership were moderately stable from grade 7 to grade 8. Alcohol use and relational aggression in grade 7 predicted changes in social preference and centrality, respectively, between grade 7 and grade 8, but these effects were moderated by gender and ethnicity. Changes in social standing from grade 7 to grade 8 were unrelated to grade 8 physical aggression, relational aggression, and alcohol use after controlling for the grade 7 corollaries of these behaviors. Results are discussed in terms of their implications for understanding links between social standing and problem behaviors during adolescence.

Peer Standing and Substance Use in Early-Adolescent Grade-Level Networks: A Short-Term Longitudinal Study

Two competing hypotheses were tested concerning the associations between current alcohol and cigarette use and measures of individual, group and network peer standing in an ethnically-diverse sample of 156 male and female adolescents sampled at two time points in the seventh grade. Findings lent greater support to the person hypothesis, with early regular substance users enjoying elevated standing amongst their peers and maintaining this standing regardless of their maintenance of or desistance from current use later in the school year. In the fall semester, users (n=20, 13%) had greater social impact, were described by their peers as more popular, and were more central to the peer network than abstainers (i.e., those who did not report current use).Conversely, in the spring semester, there were no differences between users (n=22, 13%) and abstainers in peer ratings of popularity or social impact. Notably, the spring semester users group retained fewer than half of the users from the fall semester. Further, students who had reported current use in the fall, as a group, retained their positions of elevated peer standing in the spring, compared to all other students, and continued to be rated by their peers as more popular and as having greater social impact.We discuss the findings in terms of the benefit of employing simultaneous systemic and individual measures of peer standing or group prominence, which in the case of peer-based prevention programs, can help clarify the truly influential from the “pretenders” in the case of diffusion of risk-related behaviors.

Understanding Differences in Marijuana Use Among Urban Black and Suburban White High School Students from Two U.S. Community Samples

Abstract To examine community/racial differences in adolescent marijuana use and the variations in factors underlying the observed differences, a questionnaire survey study was conducted with 9th to 12th graders (n = 1,936) from two communities in New Jersey. Marijuana use was significantly higher among suburban (mostly White) students than among their urban (mostly Black) counterparts. Significant differences in marijuana use between the two community sub-samples were explained by differences in type of risk factors, mean number of risk factors, and the strength of the association (slopes) between risk factors and marijuana use. Social-environmental factors (including positive after-school activities and negative peer influences) and, to a lesser degree, family factors (including family income, parental and sibling drug use), accounted for most community/racial differences in marijuana use

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.

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.

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.