Biomedical subjects

Laura J Bierut

Publications and source records attributed to Laura J Bierut.

At least 19 recordsLinked to original sources

PubMed2026

Engagement and Retention in Precision Public Health: A Cascade Analysis of Two Cluster Randomized Trials.

INTRODUCTION: When research fails to reach and engage all populations who might benefit from study findings, it can compromise scientific validity and ultimately health equity. Few studies have systematically examined factors driving study engagement through longitudinal intervention research. This project examined sociodemographic, geographic, and structural influences on engagement and attrition across the participation "cascade" (outreach, enrollment, retention) for two large-scale multilevel precision medicine and precision prevention trials for smoking and lung cancer screening. METHODS: Modified Poisson regression models were used to determine the factors associated with study engagement based on sociodemographic and geographical factors at each step in the cascade of participation, from initial outreach through retention at 12 months post-enrollment. Secondary analyses examined the cascade among the subset of patients who had active electronic patient portals and were approached via the portal. RESULTS: A total of 24,366 patients were approached for participation. Race, Social Vulnerability Index (SVI), insurance status, and distance from the study site were significantly associated with engagement at various points in the cascade. Black patients were more likely than White patients to be reached (48.9% vs 47.1%; p = 0.022) and to complete eligibility screening (52.8% vs. 38.4%; p < 0.001), but less likely to consent to participate (56.7% vs 69.8%; p < 0.001) and complete genetic testing (58.5% vs. 69.8%; p = 0.003). Patterns of engagement through electronic patient portal versus non-electronic recruitment channels also differed by race- and place-based factors, with Black patients being less likely than White patients to respond in the portal (8.8% vs 15.5%; p < 0.001), and patients who reside farther from the study site being more likely to respond in the portal compared to those who live closer (14.9% vs 12.5%; p < 0.001). CONCLUSIONS: These findings highlight the need for tailored, stage-specific engagement strategies to ensure representative participation in genomic and behavioral intervention research to advance the integration of genomics into public health practice.

Journal Article↗

PubMed2016

Implications of Personal Genomic Testing for Health Behaviors: The Case of Smoking.

INTRODUCTION: Direct-to-consumer personal genomic testing has the potential to influence health behaviors, including smoking. Critics of this testing highlight limited evidence to support positive behavioral benefits and caution that genomic results may provide false reassurance, leading to unhealthy behaviors. This study investigates interest in genetic risks of smoking-related diseases and changes in smoking behaviors among genomic testing consumers. METHODS: From 2012 to 2013, a longitudinal series of web surveys was conducted. A total of 1464 customers of 23andMe and Pathway Genomics completed a survey prior to viewing genomic test results, of which 1002 participants provided data on smoking behaviors 6 months after receiving results. RESULTS: At baseline, 64% of participants were never smokers, 29% were former smokers, and 7% were current smokers. Most baseline current smokers were very interested in genetic risk results for lung cancer (65%) and heart disease (72%). For lung cancer, this interest was significantly greater than former (50% very interested) and never smokers (37% very interested) (p < .0001). Even though participants were interested in smoking-related disease genetic risks, 96% reported the same smoking status at baseline and 6-month follow-up. Importantly, only 1% (n = 13/916) of former and never smokers became current smokers at 6 months and 22% (n = 14/64) of current smokers reported quitting. CONCLUSIONS: Overall, smokers show a high level of interest in genetic risks of smoking-related illnesses. The experience of receiving direct-to-consumer genomic health risks does not appear to have obvious harms related to smoking behaviors, with some potential benefits. IMPLICATIONS: In the setting of ongoing controversy surrounding direct-to-consumer genomic testing, this study provides evidence that consumers are interested in genetic risk results of smoking-related diseases. Receiving genomic testing results does not lead to smoking initiation among never smokers or reinitiation among former smokers and may be associated with a higher quit rate among current smokers at 6-month follow-up than the general population. These findings ease concerns that direct-to-consumer genomic testing could lead to false reassurance and unhealthy behaviors related to smoking.

Adolescent↗

PubMed2007

Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1.

In this study, we observed loss of heterozygosity (LOH) in human chromosomal fragment 6q25.1 in sporadic lung cancer patients. LOH was observed in 65% of the 26 lung tumors examined and was narrowed down to a 2.2-Mb region. Single-nucleotide polymorphism (SNP) analysis of genes located within this region identified a candidate gene, termed p34. This gene, also designated as ZC3H12D, C6orf95, FLJ46041, or dJ281H8.1, carries an A/G nonsynonymous SNP at codon 106, which alters the amino acid from lysine to arginine. Nearly 73% of heterozygous lung cancer tissues with LOH and the A/G SNP also exhibited loss of the A allele. In vitro clonogenic and in vivo nude mouse studies showed that overexpression of the A allele exerts tumor suppressor function compared with the G allele. p34 is located within a recently mapped human lung cancer susceptibility locus, and association of the p34 A/G SNP was tested among these families. No significant association between the less frequent G allele and lung cancer susceptibility was found. Our results suggest that p34 may be a novel tumor suppressor gene involved in sporadic lung cancer but it seems not to be the candidate familial lung cancer susceptibility gene linked to chromosomal region 6q23-25.

Alleles↗

PubMed2006

Association of GABRA2 with drug dependence in the collaborative study of the genetics of alcoholism sample.

Results from twin studies suggest that overlapping genetic factors influence alcohol dependence and illicit drug dependence. Using data from the Collaborative Study on the Genetics of Alcoholism (COGA), we examined the association between 69 SNPs in the GABAA receptor gene cluster on chromosome 4 and marijuana and illicit drug dependence, individually, and as co-occurring phenotypes with alcohol dependence. Results suggested association between marijuana dependence and illicit drug dependence with SNPs in the GABRA2 gene. Interestingly, the evidence for association previously observed with alcohol dependence came only from individuals with comorbid illicit drug dependence. There was no association with other genes in the GABAA cluster on chromosome 4 with illicit drug dependence.

Alcoholism↗

PubMed2006

The genetics of alcohol dependence.

Alcohol dependence is a common, complex disorder, which affects millions of people worldwide and causes considerable burden in terms of interpersonal and societal costs. Family, twin, and adoption studies have convincingly demonstrated that genes play an important role in the development of alcohol dependence, with heritability estimates in the range of 50% to 60% for both men and women. A number of studies are under way to identify specific genes involved in the predisposition toward alcohol dependence, and there is reason to be enthusiastic about recent progress. Several associated susceptibility genes are reviewed here, including genes involved in alcohol metabolism, as well as genes involved in GABAergic, endogenous opioid, dopaminergic, cholinergic, and serotonergic transmission. The next challenge will be to further characterize the risk associated with these susceptibility genes, examining how they may be related to comorbid disorders, developmental trajectories of risk, and potential moderation by environmental factors.

Alcohol Dehydrogenase↗

PubMed2006

Novelty seeking as a moderator of familial risk for alcohol dependence.

BACKGROUND: Disinhibitory personality traits such as high novelty seeking (NS) are moderately heritable, and individuals with substance use disorders (SUDs) frequently exhibit such traits. However, recent studies have cast doubt on the supposition that such traits are true familial risk factors for SUD and particularly for alcohol dependence. Another possibility is that familial risk interacts with personality-associated risk, in which case the association between personality and familial risk might depend on sample composition, accounting for the lack of consensus among studies to date. We examined this possibility by analyzing the association between NS and alcohol dependence in individuals at intermediate and high levels of familial risk for alcohol dependence. METHODS: Data from the Collaborative Study on the Genetics of Alcoholism, a multisite family study, were examined. Subjects were 1,111 adult siblings of alcohol-dependent index cases. Parental diagnoses of alcohol dependence and personality scores of NS from the Tridimensional Personality Questionnaire were used to predict alcohol dependence. RESULTS: A significant interaction between NS and familial risk for alcoholism was seen, such that NS was a significantly stronger predictor of alcohol dependence in subjects with one or more parents with alcohol dependence than in subjects without alcohol-dependent parents. CONCLUSIONS: Novelty seeking and familial risk interact so that the risk associated with high NS is magnified in families with parental alcohol dependence and NS is a moderator of familial risk. Accordingly, high NS is strongly associated with alcohol dependence in subjects with a parent diagnosed with alcohol dependence, but low NS may protect against the risk associated with familial alcoholism. This interaction may account for conflicting findings from studies that have examined this question previously.

Alcoholism↗

PubMed2006

Teenagers are right--parents do not know much: an analysis of adolescent-parent agreement on reports of adolescent substance use, abuse, and dependence.

BACKGROUND: Previous studies have shown that when assessing child psychopathology, parents tend to report more symptoms than children for externalizing disorders such as attention deficit hyperactivity disorder (ADHD), whereas children tend to report more symptoms for internalizing disorders such as major depression. Whether for clinical or research purposes, parents are also frequently asked to report on their children's experiences with alcohol and drugs. The purpose of this study was to analyze correspondence between adolescent and parent reports of adolescent substance use and abuse or dependence. METHODS: In the current study, 591 subjects 12 to 17 years old were interviewed using the child version of the Semi-Structured Assessment for the Genetics of Alcoholism (C-SSAGA) as part of the Collaborative Study on the Genetics of Alcoholism (COGA). One parent was also interviewed about each adolescent using the parent version of the C-SSAGA. Sensitivities, specificities, and kappa coefficients were calculated to assess parental agreement with adolescent reports of lifetime substance use and Diagnostic and Statistical Manual of Mental Disorders-Third Revision substance abuse or dependence. RESULTS: The results indicate that parents are somewhat knowledgeable about their children's use of substances, particularly those that are used most commonly. For example, 55% of adolescents who had smoked cigarettes, 50% who had used alcohol, and 47% who had used marijuana had a parent who knew that they used. However, parents were less aware of substance-related problems experienced by their offspring, agreeing with adolescent reports only 27% of the time for diagnoses of alcohol abuse or dependence and 26% of the time for diagnoses of marijuana abuse or dependence. Parent reports added few cases of substance use for 12- to 13 year-olds and essentially no cases for 16- to 17-year-olds. Parent reports added a nominal number of diagnoses of substance abuse or dependence for older adolescents. CONCLUSIONS: Whether for clinical or research purposes, the results emphasize the importance of directly assessing adolescents regarding alcohol and other substance use disorders. Furthermore, investigators should consider the specific disorder(s) being investigated and the ages of the children being studied when determining whether to include parent reports as part of study design.

Adolescent↗

PubMed2006

Cigarette smoking and the risk for alcohol use disorders among adolescent drinkers.

BACKGROUND: Cigarette smoking and alcohol use disorders (AUDs) are closely linked, but it is not clear whether higher rates of AUD among smokers are solely attributable to heavier drinking or, alternatively, whether smokers are more vulnerable to alcohol abuse and dependence than nonsmokers who drink comparable quantities. We sought to address this issue using data from a nationally representative U.S. sample of adolescents and young adults. Specifically, we analyzed the relationship between cigarette smoking, drinking, and AUDs. METHODS: Data were from the aggregated 2002 through 2004 U.S. National Survey on Drug Use and Health. Participants were randomly selected, household-dwelling adolescents and young adults (ages 12-20) from the noninstitutionalized, civilian population of the United States (N=74,836). Measurements included current DSM-IV alcohol abuse or dependence, number of drinks in the past 30 days, and past-year cigarette smoking, defined as having smoked more than 100 cigarettes across the lifetime and having smoked during the past year. RESULTS: Past-year smokers (prevalence=16.0%) drank in higher quantities than never-smokers, but were also at elevated risk for AUD when compared with never-smokers who drank equivalent quantities. The effect was observed across age groups, but was more prominent among younger adolescents. After adjusting for drinking quantity and sociodemographic variables, smokers had 4.5-fold higher odds of AUD than never-smokers [95% confidence interval (95% CI), 3.1-6.6]. Youths who reported smoking but did not cross the 100-cigarette threshold were at intermediate risk [odds ratio (OR), 2.3; 95% CI, 1.7-3.3]. Differences in AUD between smokers and never-smokers were most pronounced at lower levels of drinking. CONCLUSIONS: The results are consistent with a higher vulnerability to AUDs among smokers, compared with nonsmokers who drink equivalent quantities.

Adolescent↗

PubMed2006

Comparison of psychiatric diagnoses from interview reports with those from best-estimate procedures.

OBJECTIVE: The aim of this study was to compare psychiatric diagnoses based on interview information with those based on best-estimate procedures, to evaluate information used in such procedures, and to use 5-year follow-up data to determine whether the best-estimate diagnosis is an improvement over the interview-based diagnosis. METHOD: Psychiatric diagnoses were based on interview reports from 373 probands and 2615 relatives participating in a high-risk family study of alcoholism. The diagnosis also included clinician ratings in a best-estimate procedure of this study. RESULTS: For most diagnoses, both sensitivity and specificity, using the best-estimate diagnosis (BED) as the gold standard, were excellent, in both relatives and probands. Substance abuse was an exception, with very low sensitivity, although specificity rates were excellent. For nonsubstance diagnoses, specificity was high, but sensitivity ranged from 59% to 84% across relatives and probands. In general, BED procedures led to higher prevalence estimates than those from the interview only. In the BED process, family history data were especially useful for conduct and antisocial personality disorders. Follow-up interview data supported the fact that BED procedures led to both enhancements of, as well as errors in, diagnosis. CONCLUSIONS: Our data attest to the utility of family history information, particularly for antisocial personality disorder and conduct disorder, and indicate that, for the phenotype of substance-dependence disorder, an interview-based diagnosis alone is adequate in classifying individuals with a minimum of error. These results should be reassuring for research studies in which costs and resources required for best-estimate procedures are not affordable.

Adult↗

PubMed2005

Microsatellites versus single-nucleotide polymorphisms in linkage analysis for quantitative and qualitative measures.

BACKGROUND: Genetic maps based on single-nucleotide polymorphisms (SNP) are increasingly being used as an alternative to microsatellite maps. This study compares linkage results for both types of maps for a neurophysiology phenotype and for an alcohol dependence phenotype. Our analysis used two SNP maps on the Illumina and Affymetrix platforms. We also considered the effect of high linkage disequilibrium (LD) in regions near the linkage peaks by analysing a "sparse" SNP map obtained by dropping some markers in high LD with other markers in those regions. RESULTS: The neurophysiology phenotype at the main linkage peak near 130 MB gave LOD scores of 2.76, 2.53, 3.22, and 2.68 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively. The alcohol dependence phenotype at the main linkage peak near 101 MB gave LOD scores of 3.09, 3.69, 4.08, and 4.11 for the microsatellite, Affymetrix, Illumina, and Illumina-sparse maps, respectively. CONCLUSION: The linkage results were stronger overall for SNPs than for microsatellites for both phenotypes. However, LOD scores may be artificially elevated in regions of high LD. Our analysis indicates that appropriately thinning a SNP map in regions of high LD should give more accurate LOD scores. These results suggest that SNPs can be an efficient substitute for microsatellites for linkage analysis of both quantitative and qualitative phenotypes.

Alcoholism↗

PubMed2005

An analysis of identical single-nucleotide polymorphisms genotyped by two different platforms.

The overlap of 94 single-nucleotide polymorphisms (SNP) among the 4,720 and 11,120 SNPs contained in the linkage panels of Illumina and Affymetrix, respectively, allows an assessment of the discrepancy rate produced by these two platforms. Although the no-call rate for the Affymetrix platform is approximately 8.6 times greater than for the Illumina platform, when both platforms make a genotypic call, the agreement is an impressive 99.85%. To determine if disputed genotypes can be resolved without sequencing, we studied recombination in the region of the discrepancy for the most discrepant SNP rs958883 (typed by Illumina) and tsc02060848 (typed by Affymetrix). We find that the number of inferred recombinants is substantially higher for the Affymetrix genotypes compared to the Illumina genotypes. We illustrate this with pedigree 10043, in which 3 of 7 versus 0 of 7 offspring must be double recombinants using the genotypes from the Affymetrix and the Illumina platforms, respectively. Of the 36 SNPs with one or more discrepancies, we identified a subset that appears to cluster in families. Some of this clustering may be due to the presence of a second segregating SNP that obliterates a XbaI site (the restriction enzyme used in the Affymetrix platform), resulting in a fragment too long (>1,000 bp) to be amplified.

Female↗

PubMed2005

Description of the data from the Collaborative Study on the Genetics of Alcoholism (COGA) and single-nucleotide polymorphism genotyping for Genetic Analysis Workshop 14.

The data provided to the Genetic Analysis Workshop 14 (GAW 14) was the result of a collaboration among several different groups, catalyzed by Elizabeth Pugh from The Center for Inherited Disease Research (CIDR) and the organizers of GAW 14, Jean MacCluer and Laura Almasy. The DNA, phenotypic characterization, and microsatellite genomic survey were provided by the Collaborative Study on the Genetics of Alcoholism (COGA), a nine-site national collaboration funded by the National Institute of Alcohol and Alcoholism (NIAAA) and the National Institute of Drug Abuse (NIDA) with the overarching goal of identifying and characterizing genes that affect the susceptibility to develop alcohol dependence and related phenotypes. CIDR, Affymetrix, and Illumina provided single-nucleotide polymorphism genotyping of a large subset of the COGA subjects. This article briefly describes the dataset that was provided.

Alcoholism↗

PubMed2005

Multipoint identity-by-descent computations for single-point polymorphism and microsatellite maps.

We used the LOKI software to generate multipoint identity-by-descent matrices for a microsatellite map (with 31 markers) and two single-nucleotide polymorphism (SNP) maps to examine information content across chromosome 7 in the Collaborative Study on the Genetics of Alcoholism dataset. Despite the lower information provided by a single SNP, SNP maps overall had higher and more uniform information content across the chromosome. The Affymetrix map (578 SNPs) and the Illumina map (271 SNPs) provided almost identical information. However, increased information has a computational cost: SNP maps require 100 times as many iterations as microsatellites to produce stable estimates.

Chromosome Mapping↗

PubMed2005

Functional variant in a bitter-taste receptor (hTAS2R16) influences risk of alcohol dependence.

A coding single-nucleotide polymorphism (cSNP), K172N, in hTAS2R16, a gene encoding a taste receptor for bitter beta -glucopyranosides, shows significant association with alcohol dependence (P = .00018). This gene is located on chromosome 7q in a region reported elsewhere to exhibit linkage with alcohol dependence. The SNP is located in the putative ligand-binding domain and is associated with an increased sensitivity to many bitter beta -glucopyranosides in the presence of the N172 allele. Individuals with the ancestral allele K172 are at increased risk of alcohol dependence, regardless of ethnicity. However, this risk allele is uncommon in European Americans (minor-allele frequency [MAF] 0.6%), whereas 45% of African Americans carry the allele (MAF 26%), which makes it a much more significant risk factor in the African American population.

Black or African American↗

PubMed2005

Correlations among first-degree relatives for responses on the Self-Rating of the Effects of Alcohol Questionnaire in teenagers.

OBJECTIVE: The level of response (LR) to alcohol is an intermediate phenotype related to the alcoholism risk, with a heritability of at least 0.4 as estimated from alcohol challenge experiments. A measure of LR that can be used in adolescence at a time close to the first drinking experience, and that is less expensive than alcohol challenge experiments, is the Self-Rating of the Effects of Alcohol (SRE) Questionnaire. This questionnaire contains questions related to the number of drinks required for up to four different effects early in the drinking career ("first five" score). The familial characteristics of SRE responses have been estimated in adults; however, no study has evaluated familial and potential genetic components of the first five SRE score in adolescents. This article presents data regarding the familial nature of SRE-based scores among a sample of teenagers. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism Phase II (follow-up) Protocol, SRE scores were available on 251 females and 236 males ages 13-19 years. These analyses compare the correlations among father-offspring, mother-offspring, sibling pairs and comparable unrelated individuals. RESULTS: For the 487 subjects, correlations among first-degree relatives ranged from 0.14 to 0.22 and were all significant. Correlations among comparable unrelated pairs ranged from 0.02 to 0.06 and were nonsignificant. When males and females were evaluated separately, the pattern of results, with higher correlations among first-degree relatives than among unrelated individuals, was similar, although, perhaps reflecting fewer subjects, correlations were more variable. CONCLUSIONS: Although not providing a definitive evaluation of heritability, the results are consistent with a potential proportion of the variance related to genes for first five SRE scores of between 0.3 and 0.4. These results parallel previously published data in adults and are similar to heritability estimates for LR on alcohol challenges. The data support the potential use of the first five SRE score in adolescents as a measure of LR in genetic and environmental model-based studies in young populations for whom the evaluation of LR is taking place at a time close to the onset of drinking.

Adolescent↗

PubMed2004

Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome.

Several correlated phenotypes, alcohol dependence, major depressive syndrome, and an endophenotype of electrophysiological measurements, event-related oscillations (EROs), have demonstrated linkage on the long arm of chromosome 7. Recently, we reported both linkage and association between polymorphisms in the gene encoding the muscarinic acetylcholine receptor M2 (CHRM2) and EROs. In this study, we evaluated whether genetic variation in the CHRM2 gene is also a risk factor for the correlated clinical characteristics of alcoholism and depression. The CHRM2 gene contains a single coding exon and a large 5' untranslated region encoded by multiple exons that can be alternatively spliced. Families were recruited through an alcohol dependent proband, and multiplex pedigrees were selected for genetic analyses. We examined 11 single nucleotide polymorphisms (SNPs) spanning the CHRM2 gene in these families. Using the UNPHASED pedigree disequilibrium test (PDTPHASE), three SNPs (one in intron 4 and two in intron 5) showed highly significant association with alcoholism (P=0.004-0.007). Two SNPs (both in intron 4) were significantly associated with major depressive syndrome (P=0.004 and 0.017). Haplotype analyses revealed that the most common haplotype (>40% frequency), T-T-T (rs1824024-rs2061174-rs324650), was under-transmitted to affected individuals with alcohol dependence and major depressive syndrome. Different complementary haplotypes were over-transmitted in alcohol dependent and depressed individuals. These findings provide strong evidence that variants within or close to the CHRM2 locus influence risk for two common psychiatric disorders.

Alcoholism↗

PubMed2002

Apparent replication of suggestive linkage on chromosome 16 in the NIMH genetics initiative bipolar pedigrees.

Analyses of a replication sample of families collected as part of the National Institute of Mental Health (NIMH) Genetics Initiative for bipolar disorder provide further evidence for linkage to a region of chromosome 16. Families who had a bipolar I (BPI) proband and at least one BPI or schizoaffective, bipolar type (SABP) first-degree relative were ascertained for the purpose of identifying genes involved in bipolar affective disorder. A series of hierarchical models of affected status was used in linkage analyses. Initial genetic analyses of chromosomes 3, 5, 15, 16, 17, and 22, completed at Indiana University in 540 subjects from 97 families, suggested evidence of linkage to chromosomes 5, 16, and 22 [Edenberg et al., 1997: Am J Med Genet 74:238-246]. Genotyping was subsequently performed on these chromosomes in a replication sample of 353 individuals from 56 families. Nonparametric linkage analyses were performed using both affected relative and sibling pair methods. Analyses in the new sample on chromosome 16, using the broadest model of affected status, corroborate previously reported suggestive linkage to the marker D16S2619. Combining the initial and replication samples further increased the evidence of linkage to this region, with a peak lod score of 2.8.

Bipolar Disorder↗

PubMed2002

Similarities in the clinical characteristics related to alcohol dependence in two populations.

This report evaluates whether the characteristics associated with alcohol abuse and dependence are similar in two groups of men despite their enrollment in different research projects and the resulting differences in education and related background variables. Data regarding demographic and substance use characteristics and problems were gathered using similar research instruments from the 15-ear follow-up of 108 highly educated DSM-III-R alcohol-dependent men from the San Diego Prospective Study (Group 1) and 306 similarly diagnosed men with lower education from the Collaborative Study on the Genetics of Alcoholism (COGA ) (Group 2). Both groups of alcoholics reported high rates of alcohol-relatedproblems, a similar maximum number of drinks per day, and similar proportions of drug use/non-use, although Group 1 subjects were less likely to report alcohol withdrawal and items associated with loss of control. Thus, teachers and clinicians may be able to generalize their knowledge and experience across different groups of alcoholics, using common sense modifications of their expectations based on the general characteristics of the groups involved despite differences in background variables, including education, income, marital status, and employment.

Adult↗