An analysis of shiftwork and self-reported depressive symptoms in a police cohort from Buffalo, New York.

Shiftwork has been associated with elevated depressive symptoms; police officers frequently work shifts and may experience depressive symptoms. This study assessed the association between depressive symptoms and shiftwork in a police cohort from Buffalo, New York, USA using a repeated cross-sectional design with data collected in 2004-2009 (n = 428) and 2010-2014 (n = 261). Electronic payroll records were used to quantitatively classify officers on the day, evening, or night shift based on the shift they spent most of their working hours. Two self-reported depressive symptomology measures were used as outcomes - the Center for Epidemiological Studies - Depression (CES-D) scale and the Beck Depression Inventory (BDI). Repeated measures linear and logistic regression analyses were used to estimate least squares means or odds, respectively, of depressive symptom questionnaire scores by shiftwork category. Those working the evening/night shift had higher odds for depressive symptoms according to the BDI (based on a cut-point score of 14) than those working the day shift (OR = 4.60, 95% CI = 1.15-18.39). Similar results were observed for the evening shift group. No differences in mean CES-D or BDI scores were observed between groups for short-term shiftwork, long-term shiftwork, or shift changes. After stratifying by stress, as measured by the Perceived Stress Scale (PSS), total Impact of Events (IES), and the Spielberger Police Stress Survey (SPSS), mean values for depressive symptoms were higher in the high-stress categories regardless of shiftwork status. Further research should include biomarkers for depression, a longitudinal study design with a larger cohort, and joint effects of shiftwork and stress on depressive symptoms.

High incidence of brain and other nervous system cancer identified in two mining counties, 2001-2015.

Two counties in Montana, Deer Lodge and Silver Bow (DL/SB), have two Superfund sites, as well as an active copper and molybdenum mine in SB. The population living in proximity to these sites are exposed to additional metals and some have been shown to be neurotoxic, especially for children; thus, this study focused on the incidence of brain and other nervous system cancers. The Montana Central Tumor Registry data was used to identify the cases in DL/SB and the remaining 54 counties of Montana (comparison group). After controlling for sex, cancer stage, and year of diagnosis, we found an incidence rate ratio for DL/SB versus comparison group of 6.28 (95% CI: 2.32-17.02) for children ages birth to 4 years, and 3.95 (95% CI: 1.66-9.38) for adults age 30-34 years. The high incidence rate of the brain cancer in the two age groups requires public health action.

Impact of a 12-month Inflammation Management Intervention on the Dietary Inflammatory Index, inflammation, and lipids.

BACKGROUND AND AIMS: The objective of this study was to assess the feasibility (ability to recruit participants and develop the 12-month intervention), acceptability (retention of participants in the intervention), and impact on systemic inflammation and Dietary Inflammatory Index (DII®) scores over a 12-month DII-based intervention. METHODS: Adults were recruited to participate in a self-selection trial (intervention: n = 61, in-person classes; control: n = 34, newsletters). Classes included participatory cooking and dietary recommendations focused on consuming a plant-based diet rich in anti-inflammatory foods (spices, vegetables, etc.). Changes in markers of inflammation, lipids, and DII were analyzed using general linear models with repeated measurements. RESULTS: At 3 months, intervention participants had significantly lower DII scores (-2.66 ± 2.44) compared to controls (-0.38 ± 2.56) (p < 0.01); but not at 12 months (P = 0.10). The only biomarker to approach a significant group effect or group-by-time interaction was CRP (P = 0.11 for the group-by-time interaction). CRP decreased by -0.65 mg/L (95%CI = 0.10-1.20, P = 0.02) at 12 months in the intervention group; no significant decrease was seen for the control group. With both groups combined at 3 months, those with the greatest decrease/improvement in DII score (tertile 1) compared with those whose scores increased (tertile 3) had greater reductions in CRP (-1.09 vs. +0.52 mg/L, P = 0.04), total cholesterol (-9.38 vs. +12.02 mg/dL, P = 0.01), and LDL cholesterol (-11.99 vs. +7.16 mg/dL, P = 0.01). CONCLUSIONS: Although the intervention group had reductions in DII and CRP, main inflammation and lipid outcomes did not differ between groups. Overall, those participants with the largest reduction in DII scores had the largest reductions in CRP and LDL and total cholesterol. Future interventions may need to have more components in place to support maintenance and continued reductions in the DII. CLINICALTRIALS. GOV IDENTIFIER: NCT02382458.

Perspective: The Dietary Inflammatory Index (DII)-Lessons Learned, Improvements Made, and Future Directions.

The literature on the role of inflammation in health has grown exponentially over the past several decades. Paralleling this growth has been an equally intense focus on the role of diet in modulating inflammation, with a doubling in the size of the literature approximately every 4 y. The Dietary Inflammatory Index (DII) was developed to provide a quantitative means for assessing the role of diet in relation to health outcomes ranging from blood concentrations of inflammatory cytokines to chronic diseases. Based on literature from a variety of different study designs ranging from cell culture to observational and experimental studies in humans, the DII was designed to be universally applicable across all human studies with adequate dietary assessment. Over the past 4 y, the DII has been used in >200 studies and forms the basis for 12 meta-analyses. In the process of conducting this work, lessons were learned with regard to methodologic issues related to total energy and nutrient intake and energy and nutrient densities. Accordingly, refinements to the original algorithm have been made. In this article we discuss these improvements and observations that we made with regard to misuse and misinterpretation of the DII and provide suggestions for future developments.

Dietary patterns based on the Mediterranean diet and DASH diet are inversely associated with high aggressive prostate cancer in PCaP.

BACKGROUND: Several foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race. METHODS: Data from the population-based, case-only North Carolina-Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer. RESULTS: Higher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06). CONCLUSIONS: Higher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer.

Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study.

PURPOSE: To explore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). METHODS AND MATERIALS: Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy >6 months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4 atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiation therapy began within 15 minutes after HBO. Patients were followed for 2 years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+ years for local recurrence, distant metastases, disease-specific survival, and overall survival. RESULTS: Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14 weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5 minutes, with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per-protocol 5-year overall survival was 100%, local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO. CONCLUSIONS: While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation.

The Effects of a Park Awareness Campaign on Rural Park Use and Physical Activity.

To examine the effects of a park awareness campaign on park use in 6 community parks. One-group pretest-posttest design. Six community parks located in a South Carolina county. Children, adolescents, and adults observed in community parks. A 1-month awareness campaign that culminated in single 1.5-hour events at 6 parks in April 2011 and May 2011. The System for Observing Play and Recreation in Communities was used to objectively measure park use in May 2010 (baseline) and May 2011 (postcampaign). Zero-inflated Poisson models tested whether the number of total park users and the number of park users engaged in sedentary, walking, and vigorous activities differed by observation date. Park use was significantly greater at baseline than postcampaign (97 vs 84 users, respectively; χ = 4.69, P = .03). There were no significant differences in the number of park users engaged in sedentary (χ = 2.45, P = .12), walking (χ = 0.29, P = .59), and vigorous (χ = 0.20, P = .65) activities between baseline and postcampaign. Although only 97 and 84 people were observed across all parks at baseline and postcampaign, a total of 629 people were observed during the 6 separate 1.5-hour campaign park events. This suggests that there is potential for greater park utilization in these communities, and important questions remain on how to conduct effective awareness campaigns and how to harness interest in park events for the purpose of contributing to future community-wide physical activity and health promotion efforts.

Inflammatory potential of diet and all-cause, cardiovascular, and cancer mortality in National Health and Nutrition Examination Survey III Study.

BACKGROUND: Various dietary components have been studied in relation to overall mortality; however, little is known about the relationship between the inflammatory potential of overall diet and mortality. MATERIALS AND METHODS: We examined the association between the dietary inflammatory index (DII) and mortality in the National Health and Nutrition Examination Survey III follow-up study. The DII was computed from baseline dietary intake assessed using 24-h dietary recalls (1988-1994). Mortality was determined from the National Death Index records through 2006. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95 % confidence interval (95 % CI). During the follow-up, 2795 deaths were identified, including 1233 due to cardiovascular disease (CVD), and 615 due to cancer, 158 of which were due to digestive-tract cancers. RESULTS: Multivariate Cox proportional hazards regression analyses, adjusting for age, race, diabetes status, hypertension, physical activity, body mass index, poverty index, and smoking, revealed positive associations between higher DII scores and mortality. Comparing subjects in DII tertile 3 versus tertile 1, significant associations were noted for all-cause mortality (HRTertile3vs1 1.34; 95 % CI 1.19-1.51, P trend < 0.0001), CVD mortality (HRTertile3vs1 1.46; 95 % CI 1.18-1.81, P trend = 0.0006), cancer mortality (HRTertile3vs1 1.46; 95 % CI 1.10-1.96, P trend = 0.01), and digestive-tract cancer mortality (HRTertile3vs1 2.10; 95 % CI 1.15-3.84, P trend = 0.03). CONCLUSION: These results indicate that a pro-inflammatory diet, as indicated by higher DII scores, was associated with higher risk of all-cause, CVD, and cancer mortality.

Provider Behavior Under Global Budgeting and Policy Responses: An Observational Study on Eye Care Services in Taiwan.

Third-party payer systems are consistently associated with health care cost escalation. Taiwan's single-payer, universal coverage National Health Insurance (NHI) adopted global budgeting (GB) to achieve cost control. This study captures ophthalmologists' response to GB, specifically service volume changes and service substitution between low-revenue and high-revenue services following GB implementation, the subsequent Bureau of NHI policy response, and the policy impact. De-identified eye clinic claims data for the years 2000, 2005, and 2007 were analyzed to study the changes in Simple Claim Form (SCF) claims versus Special Case Claims (SCCs). The 3 study years represent the pre-GB period, post-GB but prior to region-wise service cap implementation period, and the post-service cap period, respectively. Repeated measures multilevel regression analysis was used to study the changes adjusting for clinic characteristics and competition within each health care market. SCF service volume (low-revenue, fixed-price patient visits) remained constant throughout the study period, but SCCs (covering services involving variable provider effort and resource use with flexibility for discretionary billing) increased in 2005 with no further change in 2007. The latter is attributable to a 30% cap negotiated by the NHI Bureau with the ophthalmology association and enforced by the association. This study demonstrates that GB deployed with ongoing monitoring and timely policy responses that are designed in collaboration with professional stakeholders can contain costs in a health insurance-financed health care system.

Structures of lipoyl synthase reveal a compact active site for controlling sequential sulfur insertion reactions.

Lipoyl cofactors are essential for living organisms and are produced by the insertion of two sulfur atoms into the relatively unreactive C-H bonds of an octanoyl substrate. This reaction requires lipoyl synthase, a member of the radical S-adenosylmethionine (SAM) enzyme superfamily. In the present study, we solved crystal structures of lipoyl synthase with two [4Fe-4S] clusters bound at opposite ends of the TIM barrel, the usual fold of the radical SAM superfamily. The cluster required for reductive SAM cleavage conserves the features of the radical SAM superfamily, but the auxiliary cluster is bound by a CX4CX5C motif unique to lipoyl synthase. The fourth ligand to the auxiliary cluster is an extremely unusual serine residue. Site-directed mutants show this conserved serine ligand is essential for the sulfur insertion steps. One crystallized lipoyl synthase (LipA) complex contains 5'-methylthioadenosine (MTA), a breakdown product of SAM, bound in the likely SAM-binding site. Modelling has identified an 18 Å (1 Å=0.1 nm) deep channel, well-proportioned to accommodate an octanoyl substrate. These results suggest that the auxiliary cluster is the likely sulfur donor, but access to a sulfide ion for the second sulfur insertion reaction requires the loss of an iron atom from the auxiliary cluster, which the serine ligand may enable.

The associations between park environments and park use in southern US communities.

PURPOSE: To document park use and park and neighborhood environment characteristics in rural communities, and to examine the relationship between park characteristics and park use. METHODS: The System for Observing Play and Recreation in Communities measured use in 42 target areas across 6 community parks in May 2010 and October 2010. Direct observation instruments were used to assess park and neighborhood environment characteristics. Logistic regression was used to determine the relationship between the condition, number of amenities, and number of incivilities in a target area with target area use. FINDINGS: Ninety-seven people were observed across all parks during May 2010 data collection and 116 people during October 2010 data collection. Low park quality index scores and unfavorable neighborhood environment characteristics were observed. There was a significant positive association between number of incivilities in a target area and target area use (OR = 1.91; 95% CI: 1.09-3.38; P = .03). CONCLUSIONS: The number of people observed using the parks in this study was low, and it was considerably less than the number observed in other studies. The objective park and neighborhood environment characteristics documented in this study provide a more comprehensive understanding of parks than other studies. Further examining the complex relationship between park and neighborhood environment characteristics and park use is important, as it can inform park administrators and city planners of characteristics that are best able to attract visitors.

Proportion of gestational diabetes mellitus attributable to overweight and obesity among non-Hispanic black, non-Hispanic white, and Hispanic women in South Carolina.

Objective was to estimate race-specific proportions of gestational diabetes mellitus (GDM) attributable to overweight and obesity in South Carolina. South Carolina birth certificate and hospital discharge data were obtained from 2004 to 2006. Women who did not have type 2 diabetes mellitus before pregnancy were classified with GDM if a diagnosis was reported in at least one data source. Relative risks (RR) and 95 % confidence intervals were calculated using the log-binomial model. The modified Mokdad equation was used to calculate population attributable fractions for overweight body mass index (BMI: 25.0-29.9 kg/m(2)), obese (30.0-34.9 kg/m(2)), and extremely obese (≥35 kg/m(2)) women after adjusting for age, gestational weight gain, education, marital status, parity, tobacco use, pre-pregnancy hypertension, and pregnancy hypertension. Overall, the adjusted RR of GDM was 1.6, 2.3, and 2.9 times higher among the overweight, obese, and extremely obese women compared to normal-weight women in South Carolina. RR of GDM for extremely obese women was higher among White (3.1) and Hispanic (3.4) women than that for Black women (2.6). The fraction of GDM cases attributable to extreme obesity was 14.0 % among White, 18.1 % among Black, and 9.6 % among Hispanic women. The fraction of GDM cases attributable to obesity was about 12 % for all racial groups. Being overweight (BMI: 25.0-29.9) explained 8.8, 7.8, and 14.4 % of GDM cases among White, Black, and Hispanic women, respectively. Results indicate a significantly increased risk of GDM among overweight, obese, and extremely obese women. The strength of the association and the proportion of GDM cases explained by excessive weight categories vary by racial/ethnic group.

A population-based dietary inflammatory index predicts levels of C-reactive protein in the Seasonal Variation of Blood Cholesterol Study (SEASONS).

OBJECTIVE: To perform construct validation of the population-based Dietary Inflammatory Index (DII) using dietary data from two different dietary assessments and serum high-sensitivity C-reactive protein (hs-CRP) as the construct validator. DESIGN: Using data derived from (i) three 24 h dietary recalls (24HR) at baseline and at the end of each subsequent quarter (i.e. up to fifteen over a year) and (ii) a 7 d dietary recall (7DDR) measured at baseline and then quarterly, regression analyses were conducted to test the effect of the DII score on serum hs-CRP as dichotomous (≤3 mg/l, >3 mg/l), while controlling for important potential confounders. SETTING: Existing data from the Seasonal Variation of Blood Cholesterol Study (SEASONS), a longitudinal observational study of healthy participants recruited in Worcester, MA, USA and participants were followed for 1 year. SUBJECTS: Participants who had at least one hs-CRP measurement over her/his 1-year participation (n 495 for 24HR, n 559 for 7DDR). RESULTS: Higher DII scores were associated with values of hs-CRP >3 mg/l (OR = 1·08; 95 % CI 1·01, 1·16, P = 0·035 for the 24HR; and OR = 1·10; 95 % CI 1·02, 1·19, P = 0·015 for the 7DDR). CONCLUSIONS: The population-based DII was associated with interval changes in hs-CRP using both the 24HR and 7DDR. The success of this first-of-a-kind attempt at relating individuals' intakes of inflammation-modulating foods using this refined DII, and the finding that there is virtually no drop-off in predictive capability using a structured questionnaire in comparison to the 24HR standard, sets the stage for use of the DII in a wide variety of other epidemiological and clinical studies.

Designing and developing a literature-derived, population-based dietary inflammatory index.

OBJECTIVE: To design and develop a literature-derived, population-based dietary inflammatory index (DII) to compare diverse populations on the inflammatory potential of their diets. DESIGN: Peer-reviewed primary research articles published through December 2010 on the effect of diet on inflammation were screened for possible inclusion in the DII scoring algorithm. Qualifying articles were scored according to whether each dietary parameter increased (+1), decreased (-1) or had no (0) effect on six inflammatory biomarkers: IL-1ß, IL-4, IL-6, IL-10, TNF-α and C-reactive protein. SETTING: The Dietary Inflammatory Index Development Study was conducted in the Cancer Prevention and Control Program of the University of South Carolina in Columbia, SC, USA from 2011 to 2012. RESULTS: A total of ≈6500 articles published through December 2010 on the effect of dietary parameters on the six inflammatory markers were screened for inclusion in the DII scoring algorithm. Eleven food consumption data sets from countries around the world were identified that allowed individuals' intakes to be expressed relative to the range of intakes of the forty-five food parameters observed across these diverse populations. Qualifying articles (n 1943) were read and scored based on the forty-five pro- and anti-inflammatory food parameters identified in the search. When fit to this composite global database, the DII score of the maximally pro-inflammatory diet was +7·98, the maximally anti-inflammatory DII score was -8·87 and the median was +0·23. CONCLUSIONS: The DII reflects both a robust literature base and standardization of individual intakes to global referent values. The success of this first-of-a-kind attempt at relating intakes of inflammation-modulating foods relative to global norms sets the stage for use of the DII in a wide variety of epidemiological and clinical studies.

Perceived environmental church support and physical activity among Black church members.

BACKGROUND: Churches are an appealing setting for implementing health-related behavior change programs. PURPOSE: The objective of the study was to examine the relationship between perceived environmental church support for physical activity (PA) and PA behaviors. METHOD: Black church members from South Carolina (n = 309) wore an Actigraph accelerometer prior to the initiation of an intervention. Relationships between moderate to vigorous PA (MVPA; counts ≥1,952), light PA (LPA; counts 100-1951), sedentary behavior (counts <100), and perceived environmental church support for PA (total, spoken informational, written informational, instrumental) were examined. Support × Gender interactions examined whether relationships differed by gender. RESULTS: The mean age was 54.0 ± 12.3 years and mean body mass index was 32.9 ± 7.2 kg/m(2). On average, participants engaged in 14.4 ± 13.7 minutes/day of MVPA, 289.8 ± 82.4 minutes/day of LPA, and were sedentary 548.9 ± 102.2 minutes/day. Total, spoken informational, and written informational church support were significantly related to higher levels of LPA and lower levels of sedentary behavior in men but not women. The relationship between written informational support and MVPA approached significance for men but not women. Instrumental church support was not associated with PA behaviors. CONCLUSION: The church environment may have an important influence on Black church members' PA behavior, particularly men's, and thus should be targeted in interventions.

Occurrence of new sexually transmitted diseases in males after HIV diagnosis.

Risk reduction following an HIV diagnosis is important for controlling the epidemic. The objective of this retrospective cohort study of 6,965 HIV-positive males was to evaluate the joint risk of new reportable STDs in males after HIV diagnosis by race/ethnicity and risk behavior. This investigation linked HIV case reports with STD surveillance, clinical care and laboratory datasets to determine new STD acquisition in HIV positive individuals.Compared to White MSM with high care engagement,Black MSM had a significantly higher rate of new reportable STDs for the full time period after HIV diagnosis, B1 year after diagnosis, and[1 year after diagnosis. High HIV care engagement was not as protective against new STD acquisition for Black MSM as it was for White MSM and reasons for this health disparity should be explored.

Racial disparities in colorectal cancer incidence by type 2 diabetes mellitus status.

PURPOSE: Type 2 diabetes mellitus (T2DM) prevalence has increased dramatically in the United States since the early 1970s. Though T2DM is known to be associated with colorectal cancer (CRC), information on racial differences in the relationship between T2DM and CRC is limited. METHODS: Using a retrospective cohort design, we compared the association between T2DM and CRC, including subsites of the colon, in African Americans (AAs) and European Americans (EAs) in South Carolina, a region with large racial disparities in rates of both diseases. A total of 91,836 individuals who were ≥30 years old on 1 January 1990 and had ≥12 months of South Carolina Medicaid eligibility between 1 January 1990 and 31 December 1995 were included in the analyses. Cancer data from 1996 to 2007 included information on anatomic subsite. RESULTS: Subjects who had T2DM (n = 6,006) were >50 % more likely to be diagnosed with colon cancer compared to those without T2DM (n = 85,681). The association between T2DM and colon cancer was higher in AAs [odds ratio (OR) = 1.72 (95 % confidence interval: 1.21, 2.46); n = 47,984] than among EAs (OR = 1.24; 0.73, 2.11; n = 43,703). Overall, individuals with T2DM were over twice as likely to be diagnosed with in situ or local colon cancer (OR = 2.12; 1.40, 3.22; n = 191) compared to those without T2DM, with a higher likelihood among AAs (OR = 2.49; 1.52, 4.09; n = 113). CONCLUSIONS: Results from a Medicaid population in a high-risk region of the United States showed an increased likelihood of CRC with T2DM and suggest a racial disparity that disfavors AAs and provides further impetus for efforts aimed at diabetes prevention in this group.

Power of a reproducing kernel-based method for testing the joint effect of a set of single-nucleotide polymorphisms.

This study explored a semi-parametric method built upon reproducing kernels for estimating and testing the joint effect of a set of single nucleotide polymorphisms (SNPs). The kernel adopted is the identity-by-state kernel that measures SNP similarity between subjects. In this article, through simulations we first assessed its statistical power under different situations. It was found that in addition to the effect of sample size, the testing power was impacted by the strength of association between SNPs and the outcome of interest, and by the SNP similarity among the subjects. A quadratic relationship between SNP similarity and testing power was identified, and this relationship was further affected by sample sizes. Next we applied the method to a SNP-lung function data set to estimate and test the joint effect of a set of SNPs on forced vital capacity, one type of lung function measure. The findings were then connected to the patterns observed in simulation studies and further explored via variable importance indices of each SNP inferred from a variable selection procedure.