ADHD subtypes and co-occurring anxiety, depression, and oppositional-defiant disorder: differences in Gordon diagnostic system and Wechsler working memory and processing speed index scores.

OBJECTIVE: Wechsler Intelligence Scale for Children Freedom-from-Distractibility/Working Memory Index (FDI/WMI), Processing Speed Index (PSI), and Gordon Diagnostic System (GDS) scores in ADHD children were examined as a function of subtype and coexisting anxiety, depression, and oppositional-defiant disorder. METHOD: Participants were 587 children with ADHD combined type (alone, with oppositional-defiant disorder, and with anxiety or depression) and ADHD inattentive type (alone and with anxiety or depression). RESULTS: Attention scores (FDI/WMI and GDS Vigilance and Distractibility) were similar and low for all groups. ADHD combined groups had greater impulsivity (GDS Delay) than ADHD inattentive groups, and ADHD inattentive groups had slower processing speed (PSI) than ADHD combined groups. Comorbidity did not affect test performance. Scores differentiated ADHD subtypes with 72% accuracy. CONCLUSION: Findings support the validity of DSM-IV ADHD combined and inattentive subtypes and the validity of the GDS, FDI/WMI, and PSI in assessing attention, impulsivity, and processing speed in children with ADHD.

Perceived risk of preterm and low-birthweight birth in the Central Pennsylvania Women's Health Study.

OBJECTIVE: Engaging women in preconception prevention may be challenging if at-risk women do not perceive increased risk. This study examined predictors of perceiving increased risk for preterm/low birthweight birth. STUDY DESIGN: Using the Central Pennsylvania Women's Health Study, a population-based sample of reproductive-age women, we analyzed whether sociodemographics, health and pregnancy history, health behaviors, attitudes, or health care utilization predicted risk perception of preterm/low-birthweight birth. RESULTS: Of the 645 women analyzed, 157 (24%) estimated their risk of preterm/low-birthweight birth to be very or somewhat likely. Higher perceived risk was associated with being underweight, previous preterm/low-birthweight birth, having a mother with previous preterm/low-birthweight birth, lower perceived severity of preterm/low birthweight, and smoking. CONCLUSIONS: Several factors known to predict preterm/low birthweight did influence risk perception in this study, whereas others did not. Further research on how these factors have an impact on participation in preconception care programs is warranted.

Mental health status among rural women of reproductive age: findings from the Central Pennsylvania Women's Health Study.

OBJECTIVES: We sought to examine variables associated with mental health among rural women of reproductive age, with particular attention given to rural area type and farm residence. METHODS: We analyzed data from the Central Pennsylvania Women's Health Study, which included a random-digit-dialed survey of women aged 18 to 45 years. Hierarchical multiple linear and logistic regression models were estimated to predict 3 mental health outcomes: score on a mental health measure, depressive symptoms, and diagnosed depression or anxiety. RESULTS: Mental health outcomes were associated with different factors. Farm residence was associated with higher mental health score, and the most isolated rural residence was associated with less diagnosed depression or anxiety. Elevated psychosocial stress was consistently significant across all models. A key stress modifier, self-esteem, was also consistently significant across models. Other variables associated with 2 of the outcomes were intimate partner violence exposure and affectionate social support. CONCLUSIONS: Farm residence may be protective of general mental health for women of reproductive age, and residence in isolated rural areas may decrease access to mental health screening and treatment, resulting in fewer diagnoses of depression or anxiety.

Women's preconceptional health and use of health services: implications for preconception care.

OBJECTIVE: To improve understanding of women's use of health care before pregnancy, by analyzing how the health status and health risks of pre- and interconceptional women are associated with health services use. DATA SOURCE: Data are from a cross-sectional random-digit dial telephone survey of a representative sample of 2002 women ages 18-45 years from the Central Pennsylvania Women's Health Study (CePAWHS). A subsample of 1,325 respondents with current reproductive capacity, classified by reproductive life stage (preconceptional or interconceptional), was analyzed. STUDY DESIGN: Bivariate and multiple logistic regression analyses were conducted to determine how health needs (including indices of health status and health risks related to adverse pregnancy outcomes) are associated with five indicators of health services use (receipt of a regular physical exam, obstetrician-gynecologist [ob/gyn] visit, receipt of a set of recommended screening services, receipt of health counseling services on general health topics, and receipt of pregnancy-related counseling), controlling for predisposing and enabling variables. PRINCIPAL FINDINGS: Only half of women at risk of pregnancy report receiving counseling about pregnancy planning in the past year. One-third of women surveyed did not receive routine physical examinations and screening services, and over half received little or no health counseling. Multivariate analyses showed that all the measures of health needs except for negative health behavior were related to some type of health services use. Psychosocial stress was associated with having a recent ob/gyn visit, with receiving general health counseling, and with receiving pregnancy planning counseling. Cardiovascular risk was positively associated with receiving general health counseling and a regular physical exam, but negatively associated with seeing an ob/gyn. Positive health behaviors were associated with receiving screening services and with receiving general health counseling. Preconceptional reproductive life stage was positively associated with receiving a regular physical exam and negatively associated with having an ob/gyn visit. CONCLUSIONS: Pre- and interconceptional women with specific health care needs may not receive appropriate health care before pregnancy. Improving pregnancy experiences and outcomes requires more comprehensive preconception health care and more preventive care before the first pregnancy.

Women's perceived control of their birth outcomes in the Central Pennsylvania Women's Health Study: implications for the use of preconception care.

PURPOSE: This study examines nonpregnant women's beliefs about whether or not they can influence their future birth outcomes with respect to the baby's health and factors associated with internal locus of control for birth outcomes. Perceived internal control of birth outcomes could be a predisposing factor for use of preconception care, which is recommended for all women of childbearing age by the Centers for Disease Control and Prevention. The overall hypothesis is that internal control of birth outcomes is a function of prior pregnancy experiences, current health status and stress levels, access to health care, and sociodemographics. METHODS: Data are from the Central Pennsylvania Women's Health Study random digit dial telephone survey of 2,002 women ages 18-45; the analytic sample is 614 nonpregnant women with current reproductive capacity who reported that they are considering a future pregnancy. Internal control of birth outcomes is measured using 1) a 4-item Internal Control of Birth Outcomes Scale, 2) a single-item measure of Preconceptional Control, and 3) a score reflecting high internal control on both of these measures. FINDINGS: In multiple logistic regression analyses, internal control of birth outcomes is positively associated with older age (35-45 vs. 18-34 years), higher education (some college or more), marital status (currently married or living with a partner), and higher self-rated physical health status on the SF-12v2 (but not mental health status or psychosocial stress). Previous adverse pregnancy outcomes and current access to health care have no association with internal control for birth outcomes. CONCLUSION: Variables associated with internal control of birth outcomes among women contemplating a future pregnancy are primarily sociodemographic and physical health related. Educational and social marketing efforts to increase women's use of preconception care may be particularly important for women who are likely to have lower internal control, including younger, less educated, unmarried, and less healthy women.

The UDP-glucuronosyltransferase 2B17 gene deletion polymorphism: sex-specific association with urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol glucuronidation phenotype and risk for lung cancer.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone is a potent and abundant procarcinogen found in tobacco smoke, and glucuronidation of its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), by UDP-glucuronosyltransferases (UGT) including UGT2B17 is an important mechanism for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone detoxification. Both copies of the UGT2B17 gene are deleted in approximately 10% of Whites and the deletion is associated with a reduction in NNAL glucuronidation activity in vitro. In this study, we examined the effects of the UGT2B17 deletion (0/0) on NNAL glucuronidation rates in a sample of 82 healthy cigarette smokers and further examined its effects on lung cancer risk in a separate case-control study. In the healthy smokers study, a lower urinary ratio of NNAL-glucuronide to NNAL was observed in women with the UGT2B17 deletion (0/0) as compared with women with either the wild-type or heterozygous genotypes (P = 0.058). There were no significant differences in this ratio by genotype in men (P = 0.597). In the case-control study of 398 lung cancer patients and 697 community controls, the UGT2B17 deletion (0/0) was associated with a significant increase in risk of lung cancer in women (odds ratio, 2.0; 95% confidence interval, 1.01-4.0). The risk for the subset of women with lung adenocarcinoma was 2.8 (95% confidence interval, 1.2-6.3). The deletion was not associated with other lung histologic types in women and was not associated with the risk for any lung histologic types in men. The association of the UGT2B17 deletion with increased lung adenocarcinoma in women is consistent with its association with decreased NNAL glucuronidation rates in women and with studies showing that NNAL is a selective inducer of lung adenocarcinoma in experimental animals.

Vaginal douching and intimate partner violence: is there an association?

OBJECTIVE: This study tests the hypothesis that vaginal douching among women of reproductive age is associated with exposure to intimate partner violence (IPV). METHODS: The data source is a cross-sectional population-based sample of 2,002 women ages 18-45 in the Central Pennsylvania Women's Health Study. The survey included measures of IPV, douching behavior, and relevant sociodemographic and health-related covariates. FINDINGS: Six percent of the sample reported experiencing any type of IPV in the past year, and 23% reported douching in the past year. IPV is significantly associated with douching after controlling for sociodemographic and health-related covariates. This finding holds for women with and without current reproductive capacity. CONCLUSIONS: This is the first study to identify an association between vaginal douching and IPV. Because vaginal douching is a risk factor for sexually transmitted infections, bacterial vaginosis, and adverse pregnancy outcomes, the findings could have important implications for prevention. Further research is needed to identify the reasons why women who have been exposed to IPV are more likely to douche.

Health status, health conditions, and health behaviors among Amish women. Results from the Central Pennsylvania Women's Health Study (CePAWHS).

We performed one of the first systematic, population-based surveys of women in Amish culture. We used these data to examine health status and health risks in a representative sample of 288 Amish women ages 18-45 living in Lancaster County, Pennsylvania, in particular for risks associated with preterm and low birthweight infants, compared with a general population sample of 2,002 women in Central Pennsylvania. Compared with women in the general population, Amish women rated their physical health approximately at the same level, but reported less stress, fewer symptoms of depression, and had higher aggregate scores for mental health. Amish women reported low levels of intimate partner violence, high levels of social support, and they perceived low levels of unfair treatment owing to gender compared with the general population. Amish women also reported higher fertility, fewer low birthweight babies, but the same number of preterm births as the general population. The findings suggest that these outcomes may be due to higher levels of social support and better preconceptional behavior among Amish women.

Individual and community predictors of preterm birth and low birthweight along the rural-urban continuum in central Pennsylvania.

CONTEXT: Preterm birth and low birthweight remain high priority public health problems and are associated with increased risk of infant mortality as well as long-term health impairments. Although 20% of all births nationally are to rural women, relatively little attention has been paid to pregnancy outcomes in rural areas relative to more urbanized areas. PURPOSE: This study examines the relationship of individual- and community-level socioeconomic, health care, and health status-related characteristics to preterm birth and low birthweight outcomes among women living in urban and various types of rural communities. METHODS: Vital record data on singleton first births to residents of a 28-county region in central Pennsylvania in 2002 (N = 11,546) were merged with zip code-level information from the census and residence in a primary care health professional shortage area. Rural-urban commuting area codes were also appended. Multiple logistic regression analyses were performed to model risks of preterm birth and low birthweight using generalized estimating equations to account for clustering within zip code. FINDINGS: Women residing in large rural city-focused areas had lower adjusted odds of both preterm birth and low birthweight as compared to urban women, controlling for individual risk factors including maternal demographic characteristics, health conditions, and prenatal care use. In contrast, risks of these adverse birth outcomes were not significantly lower among women living in more rural areas relative to those in urban communities. CONCLUSIONS: Reduced risks of preterm birth and low birthweight risk are associated with some, but not all types of rural as compared to urban communities.

Hip fracture risk among community-dwelling elderly people in the United States: a prospective study of physical, cognitive, and socioeconomic indicators.

OBJECTIVES: We determined risks of short-term (2-year) hip fracture in a nationally representative, prospective cohort of community-dwelling elderly people 70 years or older. METHODS: We used self-report data from 2 waves of the Asset and Health Dynamics Survey (n = 5630). Sample-weighted logistic regression analyses were conducted to determine risk of hip fracture in relation to several demographic, cognitive, physical, and socioeconomic indicators. RESULTS: During the 2-year study period, 102 participants reported a new hip fracture. Several indicators of physical functioning and cognitive status, including incorrect delayed word recall and inability to lift 10 lbs (4.5 kg), were significantly associated with hip fracture risk. In the final model, mobile home residents, individuals without Medicare part B insurance, and those without a high-school diploma were at more than a 2-fold risk of hip fracture. Educational level, physical functioning, and insurance status were the top 3 contributors to hip fracture risk. CONCLUSIONS: In addition to functional status measures, health insurance status, educational level, and type of residence appear to be independent predictors of hip fracture.

Preconceptional health: risks of adverse pregnancy outcomes by reproductive life stage in the Central Pennsylvania Women's Health Study (CePAWHS).

This study used population-based data to examine how health status and risks vary by reproductive life stage, with particular focus on the proximal risks for preterm birth and low birthweight (LBW) infants in preconceptional and interconceptional women. Data are from the Central Pennsylvania Women's Health Study (CePAWHS), which included a telephone survey of a representative sample of 2,002 women ages 18-45 years residing in largely rural central Pennsylvania. Women were classified according to reproductive stage--preconceptional, interconceptional, and postconceptional--on the basis of pregnancy history and reproductive capacity. Multiple indicators of health status and health risks were examined by reproductive stage, stratified by age group (ages 18-34 and ages 35-45). Results show that many risk factors varied significantly by reproductive stage and by age group within reproductive stage. Preconceptional and interconceptional women exhibited several unhealthy behaviors (e.g., binge drinking, nutritional deficits, physical inactivity). Younger pre- and interconceptional women (ages 18-34) had more gynecologic infections, some less favorable health behaviors, and more psychosocial stress than older women (ages 35-45) in the same reproductive stages. Older preconceptional women were more likely to have chronic conditions (hypertension, high cholesterol) than younger preconceptional women. Results suggest how interventions could be tailored to women's reproductive stages.

Use of susceptibility scoring in conjunction with the genotypic transmission disequilibrium test.

We explored the utility of selecting a genetically predisposed subgroup to increase the finding of a genetic signal in the Genetic Analysis Workshop 14 Collaborative Study on the Genetics of Alcoholism dataset. A subgroup of affected probands with low environmental risk exposures was defined using a susceptibility score calculated from an environmental risk model. Thirty-nine probands with highly positive scores were selected, along with their parents, for use in a genotypic transmission disequilibrium test (TDT) test. We compared the results of the genotypic TDT in this subgroup to the TDT results using all probands and their parents. For some markers, the susceptibility scoring approach resulted in smaller p-values, while for other markers, evidence for a genetic signal weakened. Further explorations into genetic and environmental population characteristics that benefit from this approach are warranted.

Using mixture models to characterize disease-related traits.

We consider 12 event-related potentials and one electroencephalogram measure as disease-related traits to compare alcohol-dependent individuals (cases) to unaffected individuals (controls). We use two approaches: 1) two-way analysis of variance (with sex and alcohol dependency as the factors), and 2) likelihood ratio tests comparing sex adjusted values of cases to controls assuming that within each group the trait has a 2 (or 3) component normal mixture distribution. In the second approach, we test the null hypothesis that the parameters of the mixtures are equal for the cases and controls. Based on the two-way analysis of variance, we find 1) males have significantly (p < 0.05) lower mean response values than females for 7 of these traits. 2) Alcohol-dependent cases have significantly lower mean response than controls for 3 traits. The mixture analysis of sex-adjusted values of 1 of these traits, the event-related potential obtained at the parietal midline channel (ttth4), found the appearance of a 3-component normal mixture in cases and controls. The mixtures differed in that the cases had significantly lower mean values than controls and significantly different mixing proportions in 2 of the 3 components. Implications of this study are: 1) Sex needs to be taken into account when studying risk factors for alcohol dependency to prevent finding a spurious association between alcohol dependency and the risk factor. 2) Mixture analysis indicates that for the event-related potential "ttth4", the difference observed reflects strong evidence of heterogeneity of response in both the cases and controls.

Comparison of type I error for multiple test corrections in large single-nucleotide polymorphism studies using principal components versus haplotype blocking algorithms.

Although permutation testing has been the gold standard for assessing significance levels in studies using multiple markers, it is time-consuming. A Bonferroni correction to the nominal p-value that uses the underlying pair-wise linkage disequilibrium (LD) structure among the markers to determine the number of effectively independent tests has recently been proposed. We propose using the number of independent LD blocks plus the number of independent single-nucleotide polymorphisms for correction. Using the Collaborative Study on the Genetics of Alcoholism LD data for chromosome 21, we simulated 1,000 replicates of parent-child trio data under the null hypothesis with two levels of LD: moderate and high. Assuming haplotype blocks were independent, we calculated the number of independent statistical tests using 3 haplotype blocking algorithms. We then compared the type I error rates using a principal components-based method, the three blocking methods, a traditional Bonferroni correction, and the unadjusted p-values obtained from FBAT. Under high LD conditions, the PC method and one of the blocking methods were slightly conservative, whereas the 2 other blocking methods exceeded the target type I error rate. Under conditions of moderate LD, we show that the blocking algorithm corrections are closest to the desired type I error, although still slightly conservative, with the principal components-based method being almost as conservative as the traditional Bonferroni correction.

Contraceptive use by diabetic and obese women.

PURPOSE: Women with chronic medical conditions are at increased risk for adverse pregnancy outcomes, yet contraceptive use by these women has not been well described. The purpose of this study was to describe contraceptive use by diabetic and overweight/obese women compared with women without these conditions. METHODS: Using cross-sectional data from the 11 states participating in the optional Family Planning Module of the Behavioral Risk Factor Surveillance System in 2000, we analyzed contraceptive use among 7,943 sexually active women of reproductive age (18-44) who were not trying to conceive. Using logistic regression techniques, we modeled the effect of diabetes and overweight/obesity on contraceptive nonuse, controlling for age, race/ethnicity, marital status, education, income, and health insurance coverage. MAIN FINDINGS: Contraceptive nonuse was reported by 1,500 (18.9%) of the total sample, 31 (25.8%) diabetic women, 371 (20.0%) overweight women, and 385 (23.4%) obese women. In the multivariable model, obesity was significantly associated with contraceptive nonuse (adjusted odds ratio [OR] 1.34, 95% confidence interval [CI] 1.16-1.55), but there were no significant differences in contraceptive nonuse for diabetic women (adjusted OR 1.23, 95% CI 0.80-1.87) or overweight women (adjusted OR 1.14, 95% CI 0.99-1.31). Older, Black, Hispanic, married, less educated, and women without health insurance were more likely to report contraceptive nonuse. CONCLUSION: Among women with need for contraception, obese women were more likely to report contraceptive nonuse than normal weight women. Because women with chronic conditions like obesity are at higher risk of pregnancy-related complications and adverse pregnancy outcomes, proper contraceptive use and unintended pregnancy avoidance is a priority.

Gastric and duodenal safety of daily alendronate.

BACKGROUND: Isolated case reports of gastric ulcers after alendronate sodium use raised concern about the gastroduodenal safety of daily alendronate. This study was conducted to estimate the excess risk of hospitalizations for gastric or duodenal perforations, ulcers, and bleeding associated with alendronate use. PARTICIPANTS AND METHODS: Study subjects were 6432 men and women, 35 years or older. The subjects were members of 8 health maintenance organizations who were dispensed alendronate from October 1995 through September 1997. There was also a group of 33 176 age-, sex-, and health maintenance organization-matched unexposed persons. Because of concerns that osteoporosis might confound the association between alendronate use and perforation, ulcer, or bleeding, a second comparison group of 9776 women, 60 years or older, who had osteoporotic fractures was assembled. Hospitalizations for gastroduodenal events were identified by discharge diagnosis codes in automated claims records, and confirmed by manual record review. RESULTS: Based on the 14 confirmed events in the alendronate group and 35 in the unexposed group, the crude incidence rate ratio of gastroduodenal perforation, ulcer, or bleeding for the alendronate cohort was 3.0. The incidence rate ratio was 1.8 (95% confidence interval, 0.8-3.9) after control for prior hospitalizations, comorbidity, and recent exposure to prescription nonsteroidal anti-inflammatory drugs and oral corticosteroids. The crude incidence ratio rate for the age, sex, and health maintenance organizations-restricted cohort of alendronate users relative to the fracture cohort was 1.1 and the adjusted incidence rate ratio was 1.1 (95% confidence interval, 0.6-2.2). CONCLUSIONS: Osteoporosis and related factors appear to play an important role in the relationship between alendronate use and confirmed gastroduodenal perforation, ulcer, or bleeding; a substantial fraction of the increased risk we observed for alendronate users in the unadjusted analysis was the result of confounding.

The impact of population heterogeneity on risk estimation in genetic counseling.

BACKGROUND: Genetic counseling has been an important tool for evaluating and communicating disease susceptibility for decades, and it has been applied to predict risks for a wide class of hereditary disorders. Most diseases are complex in nature and are affected by multiple genes and environmental conditions; it is highly likely that DNA tests alone do not define all the genetic factors responsible for a disease, so that persons classified into the same risk group by DNA testing actually could have different disease susceptibilities. Ignorance of population heterogeneity may lead to biased risk estimates, whereas additional information on population heterogeneity may improve the precision of such estimates. METHODS: Although DNA tests are widely used, few studies have investigated the accuracy of the predicted risks. We examined the impact of population heterogeneity on predicted disease risks by simulation of three different heterogeneity scenarios and studied the precision and accuracy of the risks estimated from a logistic regression model that ignored population heterogeneity. Moreover, we also incorporated information about population heterogeneity into our original model and investigated the resulting improvement in the accuracy of risk estimation. RESULTS: We found that heterogeneity in one or more categories could lead to biased estimates not only in the "contaminated" categories but also in other homogeneous categories. Incorporating information about population heterogeneity into the original model greatly improved the accuracy of risk estimation. CONCLUSIONS: Our findings imply that without thorough knowledge about genetic basis of the disease, risks estimated from DNA tests may be misleading. Caution should be taken when evaluating the predicted risks obtained from genetic counseling. On the other hand, the improved accuracy of risk estimates after incorporating population heterogeneity information into the model did point out a promising direction for genetic counseling, since more and more new techniques are being invented and disease etiology is being better understood.

Genome scan meta-analysis for hypertension.

BACKGROUND: Genome scans for hypertension have yielded inconsistent results. The non-replication of significant or suggestive linkage might be due to lack of power of individual studies. Here, we conducted a genome scan meta-analysis for hypertension in an attempt to increase statistical power and to enhance evidence of linkage. METHODS: A newly developed Genome Search Meta-analysis (GSMA) method was applied to pool the results obtained from six scans reported in five papers. RESULTS: Our analysis did not find any regions with genome-wide significant linkage to hypertension. We did identify several regions with suggestive linkage, including 2p, 5q, 6q, 8p, 9p, 9q, and 11q. CONCLUSIONS: It seems that no region has a uniformly large impact on hypertension and that susceptibility genes for hypertension may be very difficult to detect.

Analysis of gene x environment interactions in sibships using mixed models.

BACKGROUND: Gene x environment models are widely used to assess genetic and environmental risks and their association with a phenotype of interest for many complex diseases. Mixed generalized linear models were used to assess gene x environment interactions with respect to systolic blood pressure on sibships adjusting for repeated measures and hierarchical nesting structures. A data set containing 410 sibships from the Framingham Heart Study offspring cohort (part of the Genetic Analysis Workshop 13 data) was used for all analyses. Three mixed gene x environment models, all adjusting for repeated measurement and varying levels of nesting, were compared for precision of estimates: 1) all sibships with adjustment for two levels of nesting (sibs within sibships and sibs within pedigrees), 2) all sibships with adjustment for one level of nesting (sibs within sibships), and 3) 100 data sets containing random draws of one sibship per extended pedigree adjusting for one level of nesting. RESULTS: The main effects were: gender, baseline age, body mass index (BMI), hypertensive treatment, cigarettes per day, grams of alcohol per day, and marker GATA48G07A. The interaction fixed effects were: baseline age by gender, baseline age by cigarettes per day, baseline age by hypertensive treatment, baseline age by BMI, hypertensive treatment by BMI, and baseline age by marker GATA48G07A. The estimates for all three nesting techniques were not widely discrepant, but precision of estimates and determination of significant effects did change with the change in adjustment for nesting. CONCLUSION: Our results show the importance of the adjustment for all levels of hierarchical nesting of sibs in the presence of repeated measures.

Susceptibility scoring in family-based association testing.

BACKGROUND: Family-based association testing is an important part of genetic epidemiology. Tests are available to include multiple siblings, unaffected offspring, and to adjust for environmental covariates. We explore a susceptibility residual method of adjustment for covariates. RESULTS: Through simulation, we show that environmental adjustments that down-weight persons who are "destined" to be affected decrease the power to detect genetic association. We used the residual adjusted method on the Framingham Heart Study offspring data, provided for Genetic Analysis Workshop 13, and got mixed results. CONCLUSION: When the genetic effect and environmental effects are independent, a susceptibility residual method of adjustment for environmental covariates reduces the power of the association test. Further study is necessary to determine if residual adjustment is appropriate in more complex disease models.