Risk factors for inguinal hernia repair among US adults.

PURPOSE: To investigate demographic, clinical, and behavioral risk factors for undergoing inguinal hernia repair within a large and ethnically diverse cohort. METHODS: We conducted a retrospective case-control study from 2007 to 2020 on 302,532 US individuals from a large, integrated healthcare delivery system with electronic health records, who participated in a survey of determinants of health. Participants without diagnosis or procedure record of an inguinal hernia at enrollment were included. We then assessed whether demographic (age, sex, race/ethnicity), clinical, and behavioral factors (obesity status, alcohol use, cigarette smoking and physical activity) were predictors of undergoing inguinal hernia repair using survival analyses. Risk factors showing statistical significance (P < 0.05) in the univariate models were added to a multivariate model. RESULTS: We identified 7314 patients who underwent inguinal hernia repair over the study period, with a higher incidence in men (6.31%) compared to women (0.53%). In a multivariate model, a higher incidence of inguinal hernia repair was associated with non-Hispanic white race/ethnicity, older age, male sex (aHR = 13.55 [95% confidence interval 12.70-14.50]), and more vigorous physical activity (aHR = 1.24 [0.045]), and alcohol drinker status (aHR = 1.05 [1.00-1.11]); while African-American (aHR = 0.69 [0.59-0.79]), Hispanic/Latino (aHR = 0.84 [0.75-0.91]), and Asian (aHR = 0.35 [0.31-0.39]) race/ethnicity, obesity (aHR = 0.33 [0.31-0.36]) and overweight (aHR = 0.71 [0.67-0.75]) were associated with a lower incidence. The use of cigarette was significantly associated with a higher incidence of inguinal hernia repair in women (aHR 1.23 [1.09-1.40]), but not in men (aHR 0.96 [0.91-1.02]). CONCLUSION: Inguinal hernia repair is positively associated with non-Hispanic white race/ethnicity, older age, male sex, increased physical activity, alcohol consumption and tobacco use (only in women); while negatively associated with obesity and overweight status. Findings from this large and ethnically diverse study may support future prediction tools to identify patients at high risk of this surgery.

Genetic contributors to variation in alcohol consumption vary by race/ethnicity in a large multi-ethnic genome-wide association study.

Alcohol consumption is a complex trait determined by both genetic and environmental factors, and is correlated with the risk of alcohol use disorders. Although a small number of genetic loci have been reported to be associated with variation in alcohol consumption, genetic factors are estimated to explain about half of the variance in alcohol consumption, suggesting that additional loci remain to be discovered. We conducted a genome-wide association study (GWAS) of alcohol consumption in the large Genetic Epidemiology Research in Adult Health and Aging (GERA) cohort, in four race/ethnicity groups: non-Hispanic whites, Hispanic/Latinos, East Asians and African Americans. We examined two statistically independent phenotypes reflecting subjects' alcohol consumption during the past year, based on self-reported information: any alcohol intake (drinker/non-drinker status) and the regular quantity of drinks consumed per week (drinks/week) among drinkers. We assessed these two alcohol consumption phenotypes in each race/ethnicity group, and in a combined trans-ethnic meta-analysis comprising a total of 86 627 individuals. We observed the strongest association between the previously reported single nucleotide polymorphism (SNP) rs671 in ALDH2 and alcohol drinker status (odd ratio (OR)=0.40, P=2.28 × 10-72) in East Asians, and also an effect on drinks/week (beta=-0.17, P=5.42 × 10-4) in the same group. We also observed a genome-wide significant association in non-Hispanic whites between the previously reported SNP rs1229984 in ADH1B and both alcohol consumption phenotypes (OR=0.79, P=2.47 × 10-20 for drinker status and beta=-0.19, P=1.91 × 10-35 for drinks/week), which replicated in Hispanic/Latinos (OR=0.72, P=4.35 × 10-7 and beta=-0.21, P=2.58 × 10-6, respectively). Although prior studies reported effects of ADH1B and ALDH2 on lifetime measures, such as risk of alcohol dependence, our study adds further evidence of the effect of the same genes on a cross-sectional measure of average drinking. Our trans-ethnic meta-analysis confirmed recent findings implicating the KLB and GCKR loci in alcohol consumption, with strongest associations observed for rs7686419 (beta=-0.04, P=3.41 × 10-10 for drinks/week and OR=0.96, P=4.08 × 10-5 for drinker status), and rs4665985 (beta=0.04, P=2.26 × 10-8 for drinks/week and OR=1.04, P=5 × 10-4 for drinker status), respectively. Finally, we also obtained confirmatory results extending previous findings implicating AUTS2, SGOL1 and SERPINC1 genes in alcohol consumption traits in non-Hispanic whites.

Genome-wide association study identifies ABCG2 (BCRP) as an allopurinol transporter and a determinant of drug response.

The first-line treatment of hyperuricemia, which causes gout, is allopurinol. The allopurinol response is highly variable, with many users failing to achieve target serum uric acid (SUA) levels. No genome-wide association study (GWAS) has examined the genetic factors affecting allopurinol effectiveness. Using 2,027 subjects in Kaiser Permanente's Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort, we conducted a GWAS of allopurinol-related SUA reduction, first in the largest ethnic group, non-Hispanic white (NHW) subjects, and then in a stratified transethnic meta-analysis. ABCG2, encoding the efflux pump BCRP, was associated with SUA reduction in NHW subjects (P = 2 × 10(-8) ), and a missense allele (rs2231142) was associated with a reduced response (P = 3 × 10(-7) ) in the meta-analysis. Isotopic uptake studies in cells demonstrated that BCRP transports allopurinol and genetic variants in ABCG2 affect this transport. Collectively, this first GWAS of allopurinol response demonstrates that ABCG2 is a key determinant of response to the drug.