Quantifying and recommending seat belt reminder timing using naturalistic driving video data.

INTRODUCTION: To better understand the timing of when people buckle their seat belt, an analysis of a naturalistic driving study was used. The study provided a unique perspective inside of the vehicle where the entire seat belt was visible from the time the driver entered the vehicle to one minute of driving forward or 32 kph. METHOD: Seat belt buckling behavior was identified for 30 drivers. An additional 10 drives for 13 of these drivers were identified for a seat belt sequencing, which identified the points when the vehicle was put into ignition, shifted, when vehicle movement began, and when the seat belt was buckled. The speed at belt closure was also identified. The timing from ignition to buckle and to shifting into forward gear were examined to identify the speed and appropriate timing for seat belt reminders. RESULTS: The data show that drivers were buckled in over 92% of the 3,102 drives. In addition, in 70% of those total drives, the drivers were buckled before the vehicle began movement. Of greater interest for seat belt reminders/interlocks are those drives when drivers buckle after movement. When considering time from ignition to seat belt closure, the mean was 27.5 s. Because higher speeds are typically reached when traveling forward rather than reverse, it was important to know the time duration from shifting into drive to buckling. With this consideration, the mean to buckle dropped to 16.2 s. The mean speed at buckling when traveling forward was 15.3 kph. From the regression analysis, the input variables 'Age,' 'Sex,' 'Weight,' 'Environment,' and 'Weather' are significant contributors in predicting the log odds of a driver putting on seatbelt. CONCLUSIONS: With the understanding that higher speeds lead to an increased risk of injury and/or death and with the results of the analysis, a recommendation of a 30 s time from forward shift and a 25 kph (6.9 m/s) threshold for reminder systems should be implemented. The regression analysis also validates that most of the predicted seat belt buckling times are within 30 s. Practical Applications: This would reduce perception of nuisance alerts and protect the driver from higher speed unbuckled crashes. The seat belt buckling time prediction model also demonstrates good potential for developing tailored buckling warning system for different drivers.

Glycemic outcomes related to depression in adults with type 1 diabetes.

Glycemic outcomes of adults with type 1 diabetes may be affected by depression. Our aim was to compare outcomes of "depressed" (Patient Health Questionnaire-9 ⩾ 10, N = 83) to "not-depressed" matched control (Patient Health Questionnaire-2 < 3, N = 166) adults with type 1 diabetes with objective measures. The depressed group had poorer blood glucose control and, for those with glucose meter downloads, fewer glucose tests/day. The groups did not differ on glucose variability or episodes of hypoglycemia. Depression in adults with type 1 diabetes is associated with poorer glycemic control and less blood glucose monitoring. Future research should examine whether treatment of depression results in better self-care and glycemic outcomes.

Glycemic outcomes related to depression in adults with type 1 diabetes.

Glycemic outcomes of adults with type 1 diabetes may be affected by depression. Our aim was to compare outcomes of "depressed" (Patient Health Questionnaire-9 ⩾ 10, N = 83) to "not-depressed" matched control (Patient Health Questionnaire-2 < 3, N = 166) adults with type 1 diabetes with objective measures. The depressed group had poorer blood glucose control and, for those with glucose meter downloads, fewer glucose tests/day. The groups did not differ on glucose variability or episodes of hypoglycemia. Depression in adults with type 1 diabetes is associated with poorer glycemic control and less blood glucose monitoring. Future research should examine whether treatment of depression results in better self-care and glycemic outcomes.

Gene co-expression networks in peripheral blood capture dimensional measures of emotional and behavioral problems from the Child Behavior Checklist (CBCL).

The U.S. National Institute of Mental Health (NIMH) introduced the research domain criteria (RDoC) initiative to promote the integration of information across multiple units of analysis (i.e., brain circuits, physiology, behavior, self-reports) to better understand the basic dimensions of behavior and cognitive functioning underlying normal and abnormal mental conditions. Along those lines, this study examined the association between peripheral blood gene expression levels and emotional and behavioral problems in school-age children. Children were chosen from two age- and sex-matched groups: those with or without parental reports of any prior or current psychiatric diagnosis. RNA-sequencing was performed on whole blood from 96 probands aged 6-12 years who were medication-free at the time of assessment. Module eigengenes were derived using weighted gene co-expression network analysis (WGCNA). Associations were tested between module eigengene expression levels and eight syndrome scales from parent ratings on the Child Behavior Checklist (CBCL). Nine out of the 36 modules were significantly associated with at least one syndrome scale measured by the CBCL (i.e., aggression, social problems, attention problems, and/or thought problems) after accounting for covariates and correcting for multiple testing. Our study demonstrates that variation in peripheral blood gene expression relates to emotional and behavioral profiles in children. If replicated and validated, our results may help in identifying problem or at-risk behavior in pediatric populations, and in elucidating the biological pathways that modulate complex human behavior.

Exome sequencing in schizophrenia-affected parent-offspring trios reveals risk conferred by protein-coding de novo mutations.

Protein-coding de novo mutations (DNMs) are significant risk factors in many neurodevelopmental disorders, whereas schizophrenia (SCZ) risk associated with DNMs has thus far been shown to be modest. We analyzed DNMs from 1,695 SCZ-affected trios and 1,077 published SCZ-affected trios to better understand the contribution to SCZ risk. Among 2,772 SCZ probands, exome-wide DNM burden remained modest. Gene set analyses revealed that SCZ DNMs were significantly concentrated in genes that were highly expressed in the brain, that were under strong evolutionary constraint and/or overlapped with genes identified in other neurodevelopmental disorders. No single gene surpassed exome-wide significance; however, 16 genes were recurrently hit by protein-truncating DNMs, corresponding to a 3.15-fold higher rate than the mutation model expectation (permuted 95% confidence interval: 1-10 genes; permuted P = 3 × 10-5). Overall, DNMs explain a small fraction of SCZ risk, and larger samples are needed to identify individual risk genes, as coding variation across many genes confers risk for SCZ in the population.

OnabotulinumtoxinA wear-off in chronic migraine, observational cohort study.

INTRODUCTION: The current standard-of-care protocol for OnabotulinumtoxinA (BoNTA) injections consists of fixed-site injections every 12 weeks. This pattern is based on clinical practice and extrapolated from BoNTA injections for other, non-migraine-related indications. It is unclear if this protocol is optimal for chronic migraine. In clinical practice, migraine patients frequently describe a period of increased headache frequency and intensity in the few weeks preceding their next injections. In order to evaluate the duration of the clinical effect of BoNTA injections in chronic migraine, we studied the variation in headache frequency on a weekly basis during the 12-week period following treatment in a cohort of migraine patients. METHOD: 38 consecutive subjects were enrolled from an outpatient headache clinic, and asked to keep daily headache journals. 24 completed headache journals were analyzed. Headache frequency, duration and severity, as well as intake of symptomatic headache medications were recorded and compared among the different weeks. RESULTS: The time-response plot following BoNTA injection was roughly U-shaped, with 3 distinct phases: an induction phase, a maximum efficacy phase, and a wear-off phase. The time-response plot revealed that the wear-off commenced around the eighth week post injection. The mean difference in the number of headache days per week between the first and the eighth week was 1.8 (95% CI [0.670-2.830], p = 0.003). CONCLUSION: The effect of BoNTA injections on chronic migraines was not uniform throughout a 12-week period. A window of vulnerability to migraine attacks exist in the beginning and end of each cycle.

Use of a Smartphone Application to Reduce Hypoglycemia in Type 1 Diabetes: A Pilot Study.

BACKGROUND: Hypoglycemia and hypoglycemia unawareness are common in long-standing type 1 diabetes (T1D). This pilot study examined the real-world use of a smartphone application (app), which receives meter readings and logs hypoglycemic symptoms, causes, and treatments to reduce hypoglycemia. METHODS: Adults with T1D and recent hypoglycemia synchronized their glucose meter to their smartphone and used the Joslin HypoMap™ app powered by Glooko to track hypoglycemic events. At baseline, and after 6 and 12 weeks of using the app, a blinded continuous glucose monitor (CGM; Dexcom G4) was used for 2 weeks and surveys administered. RESULTS: Participants (n = 22) at baseline had mean (SD) age 43 (14) years, duration of diabetes 26 (13) years, A1c 8.0% (0.87) and 21/22 had reduced hypoglycemia awareness per Clarke Hypoglycemia Unawareness survey scores; 13 (59%) were "CGM completers" (CGM data available at baseline and follow-up). Most noncompletion related to time required/difficulties using the mobile app. After 6 weeks, 8/13 completers (62% of CGM completers, 36% of total participants) had reduced daytime minutes with glucose <54 mg/dL (mean ↓331 minutes) and 10/13 (77% of CGM completers; 45% of total participants) had reduced time ≤ 70 mg/dL (mean ↓449 minutes). This was not sustained at 12 weeks, at which time half of the completers had less time ("improved"). Five participants reported improved hypoglycemia awareness; 9 stated the app helped them better recognize hypoglycemia. CONCLUSIONS: Use of this phone app has the potential to help reduce daytime hypoglycemia in a subset of T1D adults with reduce hypoglycemia awareness; larger studies are needed.

Foot placement during error and pedal applications in naturalistic driving.

Data from a naturalistic driving study was used to examine foot placement during routine foot pedal movements and possible pedal misapplications. The study included four weeks of observations from 30 drivers, where pedal responses were recorded and categorized. The foot movements associated with pedal misapplications and errors were the focus of the analyses. A random forest algorithm was used to predict the pedal application types based the video observations, foot placements, drivers' characteristics, drivers' cognitive function levels and anthropometric measurements. A repeated multinomial logit model was then used to estimate the likelihood of the foot placement given various driver characteristics and driving scenarios. The findings showed that prior foot location, the drivers' seat position, and the drive sequence were all associated with incorrect foot placement during an event. The study showed that there is a potential to develop a driver assistance system that can reduce the likelihood of a pedal error.

Use of Telemedicine for Management of Diabetes in Correctional Facilities.

BACKGROUND: Prisoners can have difficulty obtaining subspecialty consultations. Telemedicine is used to provide diabetes consultations for residents of correctional facilities from our diabetes center. Telemedicine helps improve access to endocrinologists at reduced cost, but little outcome data are available. METHODS: A retrospective chart review of prisoners from 15 correctional facilities who received televisits for diabetes from 2011 to 2014 was performed. Demographic information, complications, medications, blood pressure, and laboratory results were collected. RESULTS: At baseline (n = 106), mean age was 44 years, duration of diabetes was 15 years, 44% had type 1 diabetes, and all were male. Only 64 of the participants had ≥2 video consultations; 58/64 had follow-up HbA1c results; and 53/58 were insulin requiring. Mean initial HbA1c was 9.3% with an average decrease of 0.5% from initial to final visit (a mean of 3.6 televisits). Patients with an initial HbA1c >9% (n = 28) had an average drop of 1.3%. Twenty-two subjects had initial elevated blood pressure; 20/22 (91%) were prescribed angiotensin-converting-enzyme-inhibitors (ACE-I)/angiotensin II receptor blockers (ARB); and 15 of these 20 (75%) had a final blood pressure <140/90 mm Hg over a mean of 3.3 televisits. 17/20 with high low-density lipoprotein (LDL) were treated with statin drugs; 15/17 (88%) had improved LDL on follow-up. Follow-up was limited by prisoner availability or visit cancellation by prison facility. CONCLUSION: Improvements in glycemic, blood pressure, and lipid control for prisoners with diabetes can be achieved with teleconsultations to correctional institutions. Given the high costs of transporting prisoners to healthcare facilities, telemedicine should be considered to help improve diabetes care for this vulnerable population.

Modeling Types of Pedal Applications Using a Driving Simulator.

OBJECTIVE: The aim of this study was to examine variations in drivers' foot behavior and identify factors associated with pedal misapplications. BACKGROUND: Few studies have focused on the foot behavior while in the vehicle and the mishaps that a driver can encounter during a potentially hazardous situation. METHOD: A driving simulation study was used to understand how drivers move their right foot toward the pedals. The study included data from 43 drivers as they responded to a series of rapid traffic signal phase changes. Pedal application types were classified as (a) direct hit, (b) hesitated, (c) corrected trajectory, and (d) pedal errors (incorrect trajectories, misses, slips, or pressed both pedals). A mixed-effects multinomial logit model was used to predict the likelihood of one of these pedal applications, and linear mixed models with repeated measures were used to examine the response time and pedal duration given the various experimental conditions (stimuli color and location). RESULTS: Younger drivers had higher probabilities of direct hits when compared to other age groups. Participants tended to have more pedal errors when responding to a red signal or when the signal appeared to be closer. Traffic signal phases and locations were associated with pedal response time and duration. The response time and pedal duration affected the likelihood of being in one of the four pedal application types. CONCLUSION AND APPLICATION: Findings from this study suggest that age-related and situational factors may play a role in pedal errors, and the stimuli locations could affect the type of pedal application.

Staff nurse confidence in their skills and knowledge and barriers to caring for patients with ostomies.

PURPOSE: Patients with ostomies often state that staff nurses display a lack of confidence in knowledge and skills related to ostomy care. This study examined the confidence and perceptions of barriers among hospital staff nurses when caring for ostomy patients. DESIGN: Descriptive, cross-sectional study. SUBJECTS AND SETTING: A convenience sample of 576 staff nurses, including 510 registered, 61 licensed practical, and 5 unspecified nurses, participated in the study. The study sample practiced at 3 sites: an academic medical center, a Veteran's Administration Center, and a not-for-profit hospital in the state of New York. METHODS: Links to a 17-question electronic survey were distributed by e-mail. The survey included items that queried demographics, availability of an ostomy nurse, ostomy training in school, and frequency of care of ostomy patients. Participants also responded to 22 statements using a 6-point Likert Scale (1 = Strongly Disagree, 6 = Strongly Agree). These statements queried confidence in providing ostomy care and perceived barriers. RESULTS: Higher confidence in ostomy care knowledge (k) and skills (s) was associated with being an LPN (P < .0001 [k], P = .003 [s]), years of nursing experience (P = .009 [k], P = .01 [s]), having ostomy training (P = .002 [k], P = .02 [s]), frequency of providing ostomy care (P < .0001 for each), and knowing how to obtain and use ostomy supplies (P < .0001 for each). The highest reported confidence was associated with emptying a pouch (mean ± SD, 5.32 ± 0.91), and the lowest was knowledge of nutrition for persons with ostomies (3.96 ± 1.21). Almost 1 in 5 respondents (18.6%) was unaware that a certified ostomy nurse practiced at their institution. CONCLUSION: Confidence of staff nurses in delivering ostomy care was higher with training and experience. Opportunities for continuing education may increase staff nurse confidence in providing ostomy care. The greatest barrier was lack of knowledge about the presence of an ostomy nurse as a resource in caring for patients.

Photoplethysmography: a simplified method for the office measurement of ankle brachial index in individuals with diabetes.

OBJECTIVE: To compare the use of photoplethysmography (PPG) and Doppler techniques to measure the ankle brachial index (ABI) for the evaluation of peripheral arterial disease (PAD) in individuals with diabetes. METHODS: Consecutive patients with diabetes (n = 103) referred for PAD evaluation had ABI measured by PPG and Doppler techniques in our diabetes center. Medical records were reviewed, and the results of the Doppler and PPG testing were compared. RESULTS: Mean age was 60 years, 57% were female, and 79% had type 2 diabetes with an average duration of 17 years. PPG readings could not be obtained in 3 individuals. Of 200 limbs evaluated, 17 (8.5%) had noncompressible (NC) vessels by both techniques. In the remaining 183 limbs, the correlation coefficient comparing the two methods was 0.864. Mean ABI values were 1.11 ± 0.14 for Doppler and 1.12 ± 0.14 for PPG. The sensitivity of PPG compared to the Doppler technique for detection of an abnormal result was 88.2%, and the specificity was 99.4%. ABI results were classified as discordant if Doppler and PPG varied by more than 0.15, placing them in different diagnostic categories (abnormal low [≤0.9], borderline [0.91-0.99], normal [1.0-1.4], or abnormal high [>1.4 or NC vessels]). There were only 4 (2%) discordant results. CONCLUSIONS: We found excellent concordance between PPG and the gold standard Doppler technique for ABI measurement in individuals with diabetes. PPG requires less training and takes less time to perform, making it highly suitable for use in an office setting.

Cleft palate, retrognathia and congenital heart disease in velo-cardio-facial syndrome: a phenotype correlation study.

OBJECTIVE: Velo-cardio-facial syndrome (VCFS) is caused by a microdeletion of approximately 40 genes from one copy of chromosome 22. Expression of the syndrome is a variable combination of over 190 phenotypic characteristics. As of yet, little is known about how these phenotypes correlate with one another or whether there are predictable patterns of expression. Two of the most common phenotypic categories, congenital heart disease and cleft palate, have been proposed to have a common genetic relationship to the deleted T-box 1 gene (TBX1). The purpose of this study is to determine if congenital heart disease and cleft palate are correlated in a large cohort of human subjects with VCFS. METHODS: This study is a retrospective chart review including 316 Caucasian non-Hispanic subjects with FISH or CGH microarray confirmed chromosome 22q11.2 deletions. All subjects were evaluated by the interdisciplinary team at the Velo-Cardio-Facial Syndrome International Center at Upstate Medical University, Syracuse, NY. Each combination of congenital heart disease, cleft palates, and retrognathia was analyzed by Chi square or Fisher exact test. RESULTS: For all categories of congenital heart disease and cleft palate or retrognathia no significant associations were found, with the exception of submucous cleft palate and retrognathia (nominal p=0.0325) and occult submucous cleft palate and retrognathia (nominal p=0.000013). CONCLUSIONS: Congenital heart disease and cleft palate do not appear to be correlated in human subjects with VCFS despite earlier suggestions from animal models. Possible explanations include modification of the effect of TBX1 by genes outside of the 22q11.2 region that may further influence the formation of the palate or heart, or the presence of epigenetic factors that may effect genes within the deleted region, modifying genes elsewhere, or polymorphisms on the normal copy of chromosome 22. Lastly, it is possible that TBX1 plays a role in palate formation in some species, but not in humans. In VCFS, retrognathia is caused by an obtuse angulation of the skull base. It is unknown if the correlation between retrognathia and cleft palate in VCFS indicates a developmental sequence related to skull morphology, or direct gene effects of both anomalies. Much work remains to be done to fully understand the complex relationships between phenotypic characteristics in VCFS.

Is More Better? - Night Vision Enhancement System's Pedestrian Warning Modes and Older Drivers.

Pedestrian fatalities as a result of vehicle collisions are much more likely to happen at night than during day time. Poor visibility due to darkness is believed to be one of the causes for the higher vehicle collision rate at night. Existing studies have shown that night vision enhancement systems (NVES) may improve recognition distance, but may increase drivers' workload. The use of automatic warnings (AW) may help minimize workload, improve performance, and increase safety. In this study, we used a driving simulator to examine performance differences of a NVES with six different configurations of warning cues, including: visual, auditory, tactile, auditory and visual, tactile and visual, and no warning. Older drivers between the ages of 65 and 74 participated in the study. An analysis based on the distance to pedestrian threat at the onset of braking response revealed that tactile and auditory warnings performed the best, while visual warnings performed the worst. When tactile or auditory warnings were presented in combination with visual warning, their effectiveness decreased. This result demonstrated that, contrary to general sense regarding warning systems, multi-modal warnings involving visual cues degraded the effectiveness of NVES for older drivers.

Spoiling the whole bunch: quality control aimed at preserving the integrity of high-throughput genotyping.

False-positive or false-negative results attributable to undetected genotyping errors and confounding factors present a constant challenge for genome-wide association studies (GWAS) given the low signals associated with complex phenotypes and the noise associated with high-throughput genotyping. In the context of the genetics of kidneys in diabetes (GoKinD) study, we identify a source of error in genotype calling and demonstrate that a standard battery of quality-control (QC) measures is not sufficient to detect and/or correct it. We show that, if genotyping and calling are done by plate (batch), even a few DNA samples of marginally acceptable quality can profoundly alter the allele calls for other samples on the plate. In turn, this leads to significant differential bias in estimates of allele frequency between plates and, potentially, to false-positive associations, particularly when case and control samples are not sufficiently randomized to plates. This problem may become widespread as investigators tap into existing public databases for GWAS control samples. We describe how to detect and correct this bias by utilizing additional sources of information, including raw signal-intensity data.

Genetic architecture of transcript-level variation in humans.

We report here the results of testing the pairwise association of 12,747 transcriptional gene-expression values with more than two million single-nucleotide polymorphisms (SNPs) in samples of European (CEPH from Utah; CEU) and African (Yoruba from Ibadan; YRI) ancestry. We found 4,677 and 5,125 significant associations between expression quantitative nucleotides (eQTNs) and transcript clusters in the CEU and the YRI samples, respectively. The physical distance between an eQTN and its associated transcript cluster was referred to as the intrapair distance. An association with 4 Mb or less intrapair distance was defined as local; otherwise, it was defined as distant. The enrichment analysis of functional categories shows that genes harboring the local eQTNs are enriched in the categories related to nucleosome and chromatin assembly; the genes harboring the distant eQTNs are enriched in the categories related to transmembrane signal transduction, suggesting that these biological pathways are likely to play a significant role in regulation of gene expression. We highlight in the EPHX1 gene a deleterious nonsynonymous SNP that is distantly associated with gene expression of ORMDL3, a susceptibility gene for asthma.

Identification of type 2 diabetes genes in Mexican Americans through genome-wide association studies.

OBJECTIVE: The objective of this study was to identify DNA polymorphisms associated with type 2 diabetes in a Mexican-American population. RESEARCH DESIGN AND METHODS: We genotyped 116,204 single nucleotide polymorphisms (SNPs) in 281 Mexican Americans with type 2 diabetes and 280 random Mexican Americans from Starr County, Texas, using the Affymetrix GeneChip Human Mapping 100K set. Allelic association exact tests were calculated. Our most significant SNPs were compared with results from other type 2 diabetes genome-wide association studies (GWASs). Proportions of African, European, and Asian ancestry were estimated from the HapMap samples using structure for each individual to rule out spurious association due to population substructure. RESULTS: We observed more significant allelic associations than expected genome wide, as empirically assessed by permutation (14 below a P of 1 x 10(-4) [8.7 expected]). No significant differences were observed between the proportion of ancestry estimates in the case and random control sets, suggesting that the association results were not likely confounded by substructure. A query of our top approximately 1% of SNPs (P < 0.01) revealed SNPs in or near four genes that showed evidence for association (P < 0.05) in multiple other GWAS interrogated: rs979752 and rs10500641 near UBQLNL and OR52H1 on chromosome 11, rs2773080 and rs3922812 in or near RALGPS2 on chromosome 1, and rs1509957 near EGR2 on chromosome 10. CONCLUSIONS: We identified several SNPs with suggestive evidence for replicated association with type 2 diabetes that merit further investigation.

Technology insight: microarrays--research and clinical applications.

For microarrays, the transition from research to clinical and diagnostic applications is well underway. Microarrays use a range of specific probes that are immobilized in known locations on a support matrix; this technique can measure levels of specific DNA, RNA and proteins, as well as carbohydrates and lipids. It is anticipated that analysis of these levels will lead to identification of biomarkers for the diagnosis, treatment and prognosis of a wide range of diseases. So far, this type of analysis has been particularly useful in clinical oncology, but the technology is being actively and successfully explored for diseases such as diabetes, endocrine tumors and endocrine modulators of tumors. There are now many commercial sources of microarrays, which have robust quality-control procedures in place. Progress will be enhanced when biomarkers can be established, statistical approaches can be refined and when we better understand the interactions of genes and of particular gene loci in disease progression.

Evidence for a susceptibility locus on chromosome 10p15 in early-onset obsessive-compulsive disorder.

BACKGROUND: The goal of this study was to identify chromosomal regions likely to contain susceptibility loci for obsessive-compulsive disorder (OCD). METHODS: We conducted a genome-wide linkage scan, with average marker spacing less than 10 centimorgans (cM), in 121 subjects from 26 families ascertained through probands with early-onset OCD. Best estimate lifetime psychiatric diagnoses were based on semistructured interviews and all other available sources of information. Parametric and nonparametric linkage analyses were conducted with GENEHUNTER+ and Allegro. Family-based association analyses were done using 35 single nucleotide polymorphisms (SNPs) in the 10p15 region. RESULTS: The maximum nonparametric log of odds (NLOD) score was 2.43 on chromosome 10p15 at position 4.37. When data from our first genome scan were added to data from this scan, the maximum NLOD score in the 10p15 region was 1.79. Association was detected on 10p15 with three adjacent SNPs, including the amino acid variant rs2271275 in the 3' region of adenosine deaminase acting on RNA 3 (ADAR3) (p < .05). CONCLUSIONS: The results provide suggestive evidence for linkage on chromosome 10p15. Evidence for association in the linkage region was found with three markers in the 3' end of ADAR3. Limitations include the lack of significant linkage and association findings when corrected for multiple testing.

Gender-specific differences in expression in human lymphoblastoid cell lines.

Women and men have different risks for certain diseases and they often respond differently to treatment. These differences could be due to the sex-specific differences in the expression of genes related to primary disease susceptibility or pharmacodynamic targets. To evaluate the sex-specific pattern of gene expression, we compared gene expression levels using a publicly available microarray dataset of 233 (115 women and 118 men) lymphoblastoid cell lines. From the 4799 probes meeting a specified minimal level of expression, 10 genes (P<0.005, permutation adjusted false discovery rate less than 50%) located on autosomal chromosomes were identified using a permutation-based approach. These genes were found to be over-represented in certain gene ontology terms of biological process (cell adhesion, apoptosis, transcription and signal transduction), and molecular function (structural molecule activity, zinc ion binding, transcription factor activity and protein binding). A Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that two known pathways are over-represented: adherens junction and cytokine-cytokine receptor interaction.