Overexpression of nucleotide metabolic enzyme DUT in hepatocellular carcinoma potentiates a therapeutic opportunity through targeting its dUTPase activity.

Uracil misincorporation during DNA replication is a major cell toxic event, of which cancer cells overcome by activating the dUTPase enzyme. The DUT gene is the only known dUTPase in human. Despite reports on common upregulations in cancers, the role of DUT in human hepatocellular carcinoma (HCC) remains largely undetermined. In this study, we investigated the mechanism underlying DUT biology in HCC and tumor susceptibility to drug targeting dUTPase. Overexpression of DUT was found in 42% of HCC tumors and correlated with advanced stage HCC. Knockout of DUT in HCC cell lines showed suppressed proliferation through cell cycle arrest and a spontaneous induction of DNA damage. A protective effect from oxidative stress was also demonstrated in both knockout and overexpression DUT assays. Transcriptome analysis highlighted the NF-κB survival signaling as the downstream effector pathway of DUT in overriding oxidative stress-induced cell death. Interestingly, stably expressed DUT in liver progenitor organoids conferred drug resistance to TKI Sorafenib. Targeting dUTPase activity by TAS-114, could potentiate suppression of HCC growth that synergized with Sorafenib for better treatment sensitivity. In conclusion, upregulated DUT represents a nucleotide metabolic weakness and therapeutic opportunity in HCC.

Alcohol drinking, especially light drinking, and depressive symptoms in adolescents.

BACKGROUND: The association of depressive symptoms with moderate and heavy drinking in adolescents have been reported in many studies, but that with light drinking is unclear. METHODS: In a 2012-13 school-based survey, 20,951 secondary school students (aged 11-20 years, 51.3 % boys) from 44 schools in Hong Kong reported their sociodemographic information, depressive symptoms, drinking patterns and other lifestyle factors. The associations of depressive symptoms with drinking status, drinking frequency and quantity, and the usual type of alcohol beverage consumed were examined using robust Poisson regression accounting for school clustering and covariates. RESULTS: The prevalence of current drinking and depressive symptoms was 13.6 % and 19.0 %, respectively. Depressive symptoms were associated with former drinking (adjusted prevalence ratio 1.48, 95 % confidence interval 1.30-1.68) and measures of light drinking: experimental drinking (1.29, 1.19-1.39), less-than-monthly drinking (1.40, 1.18-1.67) and consuming half a drink or less (1.33, 1.12-1.58), and such associations were stronger in younger adolescents. Associations were also observed for light drinking patterns of 1-2 drinks less than monthly (1.72, 1.40-2.11) and half a drink monthly (1.51, 1.21-1.88). Consuming fruit wine (1.51, 1.27-1.79) and beer (1.63, 1.42-1.88) with relatively low alcohol contents was also associated with depressive symptoms. CONCLUSIONS: Our study provided first evidence that even light drinking in terms of the amount, frequency and type of alcohol beverages or light drinking patterns such as consuming 1-2 drinks less than monthly and half a drink monthly were associated with depressive symptoms in adolescents. Our results support total alcohol abstinence in adolescents.

Serum-circulating His-tRNA synthetase inhibits organ-targeted immune responses.

His-tRNA synthetase (HARS) is targeted by autoantibodies in chronic and acute inflammatory anti-Jo-1-positive antisynthetase syndrome. The extensive activation and migration of immune cells into lung and muscle are associated with interstitial lung disease, myositis, and morbidity. It is unknown whether the sequestration of HARS is an epiphenomenon or plays a causal role in the disease. Here, we show that HARS circulates in healthy individuals, but it is largely undetectable in the serum of anti-Jo-1-positive antisynthetase syndrome patients. In cultured primary human skeletal muscle myoblasts (HSkMC), HARS is released in increasing amounts during their differentiation into myotubes. We further show that HARS regulates immune cell engagement and inhibits CD4+ and CD8+ T-cell activation. In mouse and rodent models of acute inflammatory diseases, HARS administration downregulates immune activation. In contrast, neutralization of extracellular HARS by high-titer antibody responses during tissue injury increases susceptibility to immune attack, similar to what is seen in humans with anti-Jo-1-positive disease. Collectively, these data suggest that extracellular HARS is homeostatic in normal subjects, and its sequestration contributes to the morbidity of the anti-Jo-1-positive antisynthetase syndrome.

Biallelic mutations in valyl-tRNA synthetase gene VARS are associated with a progressive neurodevelopmental epileptic encephalopathy.

Aminoacyl-tRNA synthetases (ARSs) function to transfer amino acids to cognate tRNA molecules, which are required for protein translation. To date, biallelic mutations in 31 ARS genes are known to cause recessive, early-onset severe multi-organ diseases. VARS encodes the only known valine cytoplasmic-localized aminoacyl-tRNA synthetase. Here, we report seven patients from five unrelated families with five different biallelic missense variants in VARS. Subjects present with a range of global developmental delay, epileptic encephalopathy and primary or progressive microcephaly. Longitudinal assessment demonstrates progressive cortical atrophy and white matter volume loss. Variants map to the VARS tRNA binding domain and adjacent to the anticodon domain, and disrupt highly conserved residues. Patient primary cells show intact VARS protein but reduced enzymatic activity, suggesting partial loss of function. The implication of VARS in pediatric neurodegeneration broadens the spectrum of human diseases due to mutations in tRNA synthetase genes.

Bi-allelic Mutations in Phe-tRNA Synthetase Associated with a Multi-system Pulmonary Disease Support Non-translational Function.

The tRNA synthetases catalyze the first step of protein synthesis and have increasingly been studied for their nuclear and extra-cellular ex-translational activities. Human genetic conditions such as Charcot-Marie-Tooth have been attributed to dominant gain-of-function mutations in some tRNA synthetases. Unlike dominantly inherited gain-of-function mutations, recessive loss-of-function mutations can potentially elucidate ex-translational activities. We present here five individuals from four families with a multi-system disease associated with bi-allelic mutations in FARSB that encodes the beta chain of the alpha2beta2 phenylalanine-tRNA synthetase (FARS). Collectively, the mutant alleles encompass a 5'-splice junction non-coding variant (SJV) and six missense variants, one of which is shared by unrelated individuals. The clinical condition is characterized by interstitial lung disease, cerebral aneurysms and brain calcifications, and cirrhosis. For the SJV, we confirmed exon skipping leading to a frameshift associated with noncatalytic activity. While the bi-allelic combination of the SJV with a p.Arg305Gln missense mutation in two individuals led to severe disease, cells from neither the asymptomatic heterozygous carriers nor the compound heterozygous affected individual had any defect in protein synthesis. These results support a disease mechanism independent of tRNA synthetase activities in protein translation and suggest that this FARS activity is essential for normal function in multiple organs.

Cross-sectional study on parental pro-drinking practices and adolescent alcohol drinking in Hong Kong.

OBJECTIVES: To investigate the association between parental pro-drinking practices (PPDPs) and alcohol drinking in Hong Kong Chinese adolescents. DESIGN: A cross-sectional study. SETTING: 4 randomly selected secondary schools in Hong Kong. PARTICIPANTS: 1738 students (mean age 14.6 years ± 2.0, boys 67.8%). MAIN OUTCOME MEASURES: Drinking status, drinking intention and exposure to 9 PPDPs (eg, seeing parents drunk, helping parents buy alcohol, encouraged to drink by parents) were reported by students. Logistic regression was used to compute adjusted ORs (AORs) of drinking and intention to drink by each PPDP and the number of PPDPs (0, 1-2, 3-4, 5 or above), adjusting for sociodemographic characteristics, parental drinking and school clustering. RESULTS: Nearly half (48.6%) of the students were ever-drinkers, 16.2% drank monthly (at least once per month) and 40.3% intended to drink in the next 12 months. Most PPDPs were significantly associated with ever drinking (AORs 1.40-6.20), monthly drinking (AORs 1.12-8.20) and intention to drink (AORs 1.40-5.02). Both ever and monthly drinking were most strongly associated with parental training of drinking capacity (ability to drink more without getting drunk) with AORs of 6.20 and 8.20 (both p<0.001), respectively. Adolescent drinking intention was most strongly associated with parental encouragement of drinking and training of drinking capacity with AORs of 3.19 and 5.02 (both p<0.001), respectively. CONCLUSIONS: Exposure to PPDPs was associated with ever drinking, monthly drinking and drinking intention in Hong Kong Chinese adolescents. More studies, especially prospective studies, should be conducted to confirm these results, followed by interventional studies.

Alternative splicing creates two new architectures for human tyrosyl-tRNA synthetase.

Many human tRNA synthetases evolved alternative functions outside of protein synthesis. These functions are associated with over 200 splice variants (SVs), most of which are catalytic nulls that engender new biology. While known to regulate non-translational activities, little is known about structures resulting from natural internal ablations of any protein. Here, we report analysis of two closely related, internally deleted, SVs of homodimeric human tyrosyl-tRNA synthetase (TyrRS). In spite of both variants ablating a portion of the catalytic core and dimer-interface contacts of native TyrRS, each folded into a distinct stable structure. Biochemical and nuclear magnetic resonance (NMR) analysis showed that the internal deletion of TyrRSΔE2-4 SV gave an alternative, neomorphic dimer interface 'orthogonal' to that of native TyrRS. In contrast, the internal C-terminal splice site of TyrRSΔE2-3 prevented either dimerization interface from forming, and yielded a predominantly monomeric protein. Unlike ubiquitous TyrRS, the neomorphs showed clear tissue preferences, which were distinct from each other. The results demonstrate a sophisticated structural plasticity of a human tRNA synthetase for architectural reorganizations that are preferentially elicited in specific tissues.

Sociodemographic risk factors of alcohol drinking in Hong Kong adolescents.

BACKGROUND: Adolescent drinking in Western countries has been associated with older age and high socioeconomic status, but the association with family structure was inconsistent. METHODS: In a 2012-2013 school-based survey in Hong Kong, 23,096 students (mean age 14.7 years, SD 1.8 years) completed an anonymous questionnaire. Current drinking was defined as any drinking and binge drinking as consuming at least 5 drinks on one occasion, both in the past 30 days. Multilevel logistic regression was used to examine the association of sociodemographic characteristics with current drinking, binge drinking and type of alcohol consumed. RESULTS: Current drinking was associated with age (≥ 15 vs ≤ 14 years) (adjusted OR 1.87, 95% CI 1.74 to 2.02), higher perceived family affluence versus low affluence (1.11, 1.02 to 1.21 for medium affluence; 1.55, 1.38 to 1.75 for high affluence), private housing versus public housing (1.11, 1.01 to 1.21) and non-intact family versus intact family (1.31, 1.19 to 1.45 for separated/divorced parents; 1.40, 1.21 to 1.62 for one or both deceased parents). Similar risk factors were observed for binge drinking. Girls were more likely to drink fruit wine (1.48, 1.36 to 1.62), while they were less likely to drink beer (0.85, 0.79 to 0.92) and spirits (0.69, 0.54 to 0.87). Students who reported high family affluence were more likely to drink wine (1.91, 1.59 to 2.30) and spirits (2.23, 1.54 to 3.24). CONCLUSIONS: Generally, adolescents who were older and had higher socioeconomic status were more likely to drink. High family affluence was associated with wine and spirits drinking. Beer and spirits were preferred more by boys, and fruit wine by girls. These results indicated high-risk groups for adolescent alcohol interventions.

Exposure to secondhand smoke from neighbours and respiratory symptoms in never-smoking adolescents in Hong Kong: a cross-sectional study.

OBJECTIVES: To investigate secondhand smoke (SHS) exposure at home from neighbours in Hong Kong adolescents and its association with respiratory symptoms in never-smokers. DESIGN: A cross-sectional study. SETTING: 79 randomly selected secondary schools in Hong Kong. PARTICIPANTS: 61,810 secondary 1 (USA grade 7) to 7 students, in which 50,762 never-smokers were identified and included in the analysis of the association between SHS exposure at home from neighbours and respiratory symptoms. MAIN OUTCOME MEASURES: Smoking status, family smoking status, SHS exposure at home from inside the home and from neighbours in the past 7 days, respiratory symptoms and sociodemographic characteristics were reported. Adjusted ORs (AORs) of respiratory symptoms for SHS exposure from the 2 sources in never-smokers were calculated using logistic regression. RESULTS: In all students, 33.2% were exposed to SHS at home, including 16.2% from inside the home only, 10.0% from neighbours only and 7.0% from both. The prevalence of SHS exposure from neighbours was 17.1%, including 13.5% for 1-4 days/week and 3.6% for 5-7 days/week. In never-smokers (n=50,762), respiratory symptoms were significantly associated with SHS exposure from neighbours with AORs (95% CI) of 1.29 (1.20 to 1.39) for any exposure (p<0.001), 1.21 (1.12 to 1.31) for 1-4 days/week (p<0.001) and 1.63 (1.44 to 1.86) for 5-7 days/week (p<0.001) (P for trend <0.001). Compared with no SHS exposure at home from any source, the AORs were 1.16 (1.07 to 1.25) for SHS from inside the home only (p<0.001), 1.20 (1.11 to 1.31) from neighbours only (p<0.001), and 1.74 (1.56 to 1.94) from both (p<0.001). CONCLUSIONS: SHS exposure at home from neighbours was prevalent in Hong Kong adolescents, and was associated with respiratory symptoms in never-smokers. SHS exposure at home may be underestimated by ignoring the neighbouring source. Smoke-free housing policy is needed to protect children and adolescents from harms of SHS.

Correlates of pro-drinking practices in drinking parents of adolescents in Hong Kong.

INTRODUCTION AND AIMS: Parental alcohol-related practices are important risk factors of adolescent drinking, but little is known about the factors associated with these parental pro-drinking practices (PPDPs). We investigated the correlates of 9 PPDPs in drinking parents of adolescents in Hong Kong. METHODS: A total of 2200 students (age 14.8±2.0; boys 63.2%) participated in a school-based cross-sectional survey in 2012. Analysis was restricted to 1087 (61.8%) students with at least 1 drinking parent as PPDPs were much more common in these families. Logistic regression was used to identify correlates of each PPDP. RESULTS: Among 1087 students, the prevalence of PPDPs ranged from 8.2% for training drinking capacity to 65.7% for seeing parents drink. Only 14.8% of students had not experienced any of these practices. More frequent maternal drinking predicted parental training of drinking capacity. Older age predicted helping parents buy alcohol and parental encouragement of drinking. Adolescent girls were more likely to have received parental training of drinking capacity than boys. Higher perceived family affluence was associated with hearing parents saying benefits of drinking, and helping parents open bottle and pour alcohol. CONCLUSIONS: PPDPs were associated with parental drinking frequency and various socio-demographic factors. These results have implications on alcohol control programmes involving parents to tailor messages for reducing PPDPs based on the characteristics of adolescents and parents.

Hong Kong Chinese adolescents' self-reported smoking and perceptions of parenting styles.

BACKGROUND: Adolescent smoking has been associated with general parenting style, although potential differences between fathers and mothers were seldom investigated, especially in non-Western populations. PURPOSE: The aim of this study is to investigate associations between Hong Kong adolescents' smoking and their perceptions of paternal and maternal parenting styles. METHOD: In a school-based survey in 2006-2007, 33,408 adolescents (44.6 % boys; mean age 14.5 ± 1.3 years) provided information on smoking and the frequency of care and control by each parent, who was classified into one of four adolescent-reported parenting styles: authoritative (high care, high control), authoritarian (low care, high control), permissive (high care, low control), or neglectful (low care, low control). Logistic regression was used to calculate adjusted odds ratios (AORs) of current smoking (past 30 days) for parenting variables, considering potential effect modification by age, sex and parental smoking. RESULTS: Maternal care and control were strongly and significantly associated with lower odds of adolescent current smoking. However, such association was weak for paternal care and observed only in girls. Conversely, paternal control was positively associated with current smoking, especially if the father smoked. The lowest AORs of current smoking were associated with authoritative mothers, permissive fathers and combinations of maternal and paternal parenting styles with an authoritative mother whether or not the father was authoritative. CONCLUSION: Maternal care, control and authoritative parenting were associated with lower odds of adolescent smoking in Hong Kong. Paternal care was only weakly associated with lower odds of adolescent smoking, and paternal control was even associated with higher odds of smoking.

Alcohol drinking and pro-drinking practices in parents of Hong Kong adolescents.

AIMS: We investigated the prevalence of various parental pro-drinking practices and its association with parental drinking status. METHODS: A school-based survey was completed by 2200 students (mean age 14.8, SD 2.0; boys 51.4%) from 4 randomly selected secondary schools in Hong Kong. Students reported whether they had ever experienced each of nine parental pro-drinking practices (PPDPs). RESULTS: Overall, 67.5% of students reported at least one PPDP, but the prevalence was much higher if both parents were drinkers (89.0%) compared with non-drinkers (38.8%). The adjusted odds ratio (AOR) (95% CI) of experiencing at least one PPDP was 6.79 (4.98, 9.26) if either parent drank and 15.71 (10.50, 23.50) if both drank compared with none (P for trend <0.001). Compared with non-drinking, the AORs (95% CI) of experiencing at least one PPDP for occasional drinking and frequent drinking were 6.72 (5.03, 8.98) and 18.11 (9.88, 33.18) in fathers (P for trend <0.001), and 7.33 (5.15, 10.44) and 5.33 (1.98, 14.45) in mothers. CONCLUSION: The prevalence of PPDPs was generally low in non-drinking parents, but increased dramatically with the number of drinking parents and the frequency of paternal drinking.

Human tRNA synthetase catalytic nulls with diverse functions.

Genetic efficiency in higher organisms depends on mechanisms to create multiple functions from single genes. To investigate this question for an enzyme family, we chose aminoacyl tRNA synthetases (AARSs). They are exceptional in their progressive and accretive proliferation of noncatalytic domains as the Tree of Life is ascended. Here we report discovery of a large number of natural catalytic nulls (CNs) for each human AARS. Splicing events retain noncatalytic domains while ablating the catalytic domain to create CNs with diverse functions. Each synthetase is converted into several new signaling proteins with biological activities "orthogonal" to that of the catalytic parent. We suggest that splice variants with nonenzymatic functions may be more general, as evidenced by recent findings of other catalytically inactive splice-variant enzymes.

Secreted histidyl-tRNA synthetase splice variants elaborate major epitopes for autoantibodies in inflammatory myositis.

Inflammatory and debilitating myositis and interstitial lung disease are commonly associated with autoantibodies (anti-Jo-1 antibodies) to cytoplasmic histidyl-tRNA synthetase (HisRS). Anti-Jo-1 antibodies from different disease-afflicted patients react mostly with spatially separated epitopes in the three-dimensional structure of human HisRS. We noted that two HisRS splice variants (SVs) include these spatially separated regions, but each SV lacks the HisRS catalytic domain. Despite the large deletions, the two SVs cross-react with a substantial population of anti-Jo-l antibodies from myositis patients. Moreover, expression of at least one of the SVs is up-regulated in dermatomyositis patients, and cell-based experiments show that both SVs and HisRS can be secreted. We suggest that, in patients with inflammatory myositis, anti-Jo-1 antibodies may have extracellular activity.

Physical activity and constipation in Hong Kong adolescents.

OBJECTIVE: To examine the association of constipation with exercise, non-exercise physical activity, and sedentary behaviours in Hong Kong adolescents. METHODS: In 2006-2007, 42 secondary schools were randomly selected to participate in the Hong Kong Student Obesity Surveillance (HKSOS) project. A total of 33692 Form 1-7 students (44.9% boys; mean age 14.8, SD 1.9 years) completed an anonymous questionnaire on lifestyle behaviours. Constipation was defined as a frequency of evacuation of less than once every two days. Exercise (moderate-to-vigorous levels) and non-exercise physical activity (NEPA) were each considered insufficient when less than 1 hour per day, and sedentary behaviours were considered excessive when over 4 hours per day. Logistic regression was used to calculate adjusted odds ratio (AOR) for constipation in relation to exercise, NEPA, and sedentary behaviours, adjusting for potential confounders. RESULTS: Constipation was identified in 15.6% (95% CI 15.2% - 16.0%) of adolescents overall, 14.0% in those with sufficient exercise and 19.6% in those without. Constipation was associated with insufficient exercise (AOR 1.26, 95% CI 1.16 - 1.36), insufficient NEPA 1.21 (1.10 - 1.33) and excessive sedentary behaviours (1.25, 1.17 - 1.34). Compared with having none of the above 3 inactive behaviours, increasing AORs of constipation were observed for having 1 (AOR 1.23), 2 (AOR 1.57) and 3 (AOR 1.88) inactive behaviours (p for trend <0.001). CONCLUSIONS: Constipation was associated with insufficient physical activity and excessive sedentary behaviours among Chinese adolescents with a dose-response relation. If the association is causal, constipation could be prevented by promotion of physical activity.

Longitudinal relations of perceived availability of neighborhood sport facilities with physical activity in adolescents: an analysis of potential moderators.

BACKGROUND: Little is known about the longitudinal relations of environment attributes and leisure-time physical activity (PA) in adolescents, and the moderating effects of individual characteristics. This study examined the longitudinal association of the perceived availability of neighborhood sport facilities with leisure-time PA, and the potential moderating effects of age, past PA behavior, and weight status in adolescents. METHODS: Among 20,933 follow-up subjects (60.9% of 34,369 baseline subjects), 9993 from 32 Hong Kong secondary schools were successfully matched with baseline (mean duration 16 months; SD 1.7) and had complete information. At baseline and follow-up, respondents reported their leisure-time PA, weight, height, and the presence of sport facilities in the neighborhood. RESULTS: Increased perceived availability of sport facilities from baseline to follow-up predicted more leisure-time PA at follow-up (ß = 1.029; 95% CI: 1.0111.047) overall. This effect was modified by baseline PA, with a significant effect observed only among those who had engaged in leisure-time PA more than 3 times a week. CONCLUSIONS: Increasing awareness of neighborhood sport facilities or building more such facilities may help active adolescents maintain or increase their leisure-time PA. However, more comprehensive multilevel interventions that aim at enhancing potential social, personal, and environmental PA-related factors may be needed to motivate inactive adolescents.

Assessment of weight-related factors of adolescents by private practitioners.

BACKGROUND: Few studies have examined how common physicians assess various weight-related variables and patient characteristics that predict such assessments based on adolescents' reports. We aimed to examine how common adolescents received weight-related physical measurements and lifestyle enquiries (dietary habits and physical activity) from private practitioners and to identify factors associated with these assessments. METHODS: In the Hong Kong Student Obesity Surveillance (HKSOS) project, 33692 students (44.9% boys; mean age 14.8, SD 1.9 years, age range 11-18) from 42 randomly selected schools completed an anonymous questionnaire. The students were asked "In the past 12 months, has any private practitioners (or their nurses) measured or asked about these items?" Response options included height, weight, waist circumference (WC), blood pressure (BP), BMI, diet, and physical activity. Weight status was based on self-reported weight and height. Logistic regression was used to identify student characteristics associated with each assessment. Analyses were conducted using STATA 10.0. RESULTS: Among 13283 students who had doctor consultations in the past 12 months, 37.9% received physical measurements or lifestyle enquiries, with weight (20.8%), height (16.8%) and blood pressure (11.5%) being the most common, followed by diet (8.1%), BMI (6.3%), WC and physical activity (both 4.6%). In general, adolescents who were female, older, underweight or overweight/obese, had parents with higher education level, and had actively asked private practitioners for advice about weight were more likely to receive assessments of weight-related factors. CONCLUSIONS: Weight-related factors in adolescents were infrequently assessed by private practitioners in Hong Kong. Generally, unhealthy weight, higher parental education and advice-seeking by adolescents predicted these assessments.

Regulated capture by exosomes of mRNAs for cytoplasmic tRNA synthetases.

Although tRNA synthetases are enzymes that catalyze the first step of translation in the cytoplasm, surprising functions unrelated to translation have been reported. These studies, and the demonstration of novel activities of splice variants, suggest a far broader reach of tRNA synthetases into cell biology than previously recognized. Here we show that mRNAs for most tRNA synthetases can be detected in exosomes. Also detected in exosomes was an mRNA encoding a unique splice variant that others had associated with prostate cancer. The exosomal mRNAs encoding the native synthetase and its cancer-associated splice variant could be translated in vitro and in mammalian cells into stable proteins. Other results showed that selection by exosomes of the splice variant mRNA could be regulated by an external stimulus. Thus, a broad and diverse regulated pool of tRNA synthetase-derived mRNAs is packaged for genetic exchange.

Alcohol consumption and sleep problems in Hong Kong adolescents.

OBJECTIVE: We aimed to investigate the relationship between alcohol consumption and sleep problems among Hong Kong adolescents. METHODS: In the 2006 and 2007 Hong Kong Student Obesity Surveillance project, 33,692 secondary students completed an anonymous questionnaire on lifestyles and health. Alcohol consumption was categorized as nondrinkers (reference group), those who drank less than 1day per week (less than weekly drinkers), and those who drank 1 to 7 days per week (weekly drinkers, including some daily drinkers). Students reported if they had any sleep problems in the past 30 days, including difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), early morning awakening (EMA), snoring, and difficulty breathing during sleep (DBS). Insomnia was defined as any reports of DIS, DMS, or EMA. Logistic regression was used to assess the association between alcohol and each sleep problem. Multiple imputations were used to impute missing data. RESULTS: Compared with nondrinkers, less than weekly and weekly drinkers were more likely to report snoring with adjusted odds ratios (AOR) of 1.64 (95% confidence interval [CI], 1.40-1.92) and 1.82 (95% CI, 1.55-2.14), respectively (P<.001). The corresponding figures were 1.24 (95% CI, 1.02-1.50) and 1.50 (95% CI, 1.24-1.82) for DBS (P<.001) and 1.12 (95% CI, 1.02-1.22) and 1.15 (95% CI, 1.04-1.27) for insomnia (P=.002). Weekly drinking was positively associated with DMS but negatively associated with DIS and EMA. Less than weekly drinking was positively associated with DIS, DMS, and EMA. CONCLUSIONS: Both less than weekly drinking and weekly drinking were associated with snoring, DBS, and insomnia. The association of individual symptoms of insomnia with drinking varied with the frequency of consumption.