These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

The ubiquity and consequences of childhood growth stunting (<-2 SD in height-for-age Z score, HAZ) in rural areas of low-income nations has galvanized research into the reversibility of stunting, but the shortage of panel data has hindered progress. Using panel data from a native Amazonian society of foragers-farmers in Bolivia (Tsimane'), we estimate rates of catch-up growth for stunted children. One hundred forty-six girls and 158 boys 2 < or = age < or = 7 were measured annually during 2002-2006. Annual Delta height in cm and in HAZ were regressed separately against baseline stunting and control variables related to attributes of the child, mother, household, and village. Children stunted at baseline had catch-up growth rates 0.11 SD/year higher than their nonstunted age and sex peers, with a higher rate among children farther from towns. The rate of catch up did not differ by the child's sex. A 10% rise in household income and an additional younger sibling lowered by 0.16 SD/year and 0.53 SD/year the rate of growth. Results were weaker when measuring Delta height in cm rather than in HAZ. Possible reasons for catch-up growth include (a) omitted variable bias, (b) parental reallocation of resources to redress growth faltering, particularly if parents perceive the benefits of redressing growth faltering for child school achievement, and (c) developmental plasticity during this period when growth rates are most rapid and linear growth trajectories have not yet canalized.

Genome-wide association studies of obesity measures have identified associations with single nucleotide polymorphisms (SNPs). However, no large-scale evaluation of gene-environment interactions has been performed. We conducted a search of gene-environment (G×E) interactions in post-menopausal African-American and Hispanic women from the Women’s Health Initiative SNP Health Association Resource GWAS study. Single SNP linear regression on body mass index (BMI) and waist-to-hip circumference ratio (WHR) adjusted for multidimensional-scaling-derived axes of ancestry and age was run in race-stratified data with 871,512 SNPs available from African-Americans (N=8,203) and 786,776 SNPs from Hispanics (N=3,484). Tests of G×E interaction at all SNPs for recreational physical activity (met-hrs/wk), dietary energy intake (kcal/day), alcohol intake (categorical), cigarette smoking years, and cigarette smoking (ever vs. never) were run in African-Americans and Hispanics adjusted for ancestry and age at interview, followed by meta-analysis of G×E interaction terms. The strongest evidence for concordant G×E interactions in African-Americans and Hispanics was for smoking and marker rs10133840 (Q statistic P=0.70, beta=−0.01, P=3.81×10−7) with BMI as the outcome. The strongest evidence for G×E interaction within a cohort was in African-Americans with WHR as outcome for dietary energy intake and rs9557704 (SNP×kcal =−0.04, P=2.17×10−7). No results exceeded the Bonferroni–corrected statistical significance threshold.

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Growing evidence suggests that economic inequality in a community harms the health of a person. Using panel data from a small-scale, preindustrial rural society, we test whether individual wealth rank and village wealth inequality affects self-reported poor health in a foraging-farming native Amazonian society. A person's wealth rank was negatively but weakly associated with self-reported morbidity. Each step up/year in the village wealth hierarchy reduced total self-reported days ill by 0.4 percent. The Gini coefficient of village wealth inequality bore a positive association with self-reported poor health that was large in size, but not statistically significant. We found small village wealth inequality, and evidence that individual economic rank did not change. The modest effects may have to do with having used subjective rather than objective measures of health, having small village wealth inequality, and with the possibly true modest effect of a person's wealth rank on health in a small-scale, kin-based society. Finally, we also found that an increase in mean individual wealth by village was related to worse self-reported health. As the Tsimane' integrate into the market economy, their possibilities of wealth accumulation rise, which may affect their well-being. Our work contributes to recent efforts in biocultural anthropology to link the study of social inequalities, human biology, and human-environment interactions.

BackgroundThe majority of hypertensive individuals require combination antihypertensive therapy to achieve adequate blood pressure (BP) control. This study aimed to identify genetic variants associated with uncontrolled BP on combination therapy with a thiazide diuretic and a β‐blocker.Methods and ResultsA genome‐wide association study of uncontrolled BP on combination therapy was conducted among 314 white participants of the PEAR (Pharmacogenomic Evaluation of Antihypertensive Responses) trial. Multivariable logistic regression analysis was used. Genetic variants meeting a suggestive level of significance (P<1.0E‐05) were tested for replication in an external cohort, INVEST (International Verapamil‐SR Trandolapril study). We also examined genome‐wide variant associations with systolic and diastolic BP response on combination therapy and tested for replication. We discovered a single nucleotide polymorphism, the rs261316 major allele, at chromosome 15 in the gene ALDH1A2 associated with an increased odds of having uncontrolled BP on combination therapy (odds ratio: 2.56, 95% confidence interval, 1.69–3.88, P=8.64E‐06). This single nucleotide polymorphism replicated (odds ratio: 1.86, 95% confidence interval, 1.35–2.57, P=0.001) and approached genome‐wide significance in the meta‐analysis between discovery and replication cohorts (odds ratio: 2.16, 95% confidence interval, 1.63–2.86, P=8.60E‐08). Other genes in the region surrounding rs261316 (ALDH1A2) include AQP9 and LIPC.ConclusionsA single nucleotide polymorphism in the gene ALDH1A2 may be associated with uncontrolled BP following treatment with a thiazide diuretic/β‐blocker combination.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00246519.

Background and Purpose Functional polymorphisms (Ser49Gly and Arg389Gly) in ADRB1 have been associated with cardiovascular and β-blocker response outcomes. Herein we examined associations of these polymorphisms with Major Adverse Cardiovascular Events (MACE), with and without stratification by β-blocker treatment in patients with a history of stroke. Methods 926 participants of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial’s genetic substudy with hypertension were included. MACE included stroke, myocardial infarction, and all-cause death. Kaplan-Meier and multivariable Cox regression analyses were used. Because the primary component of MACE was ischemic stroke, we tested the association of Ser49Gly with ischemic stroke among 41,475 individuals of European and African ancestry in the NINDS Stroke Genetics Network (SiGN). Results MACE was higher in carriers of the Gly49 allele than those with the Ser49Ser genotype (10.5% vs. 5.4%, log-rank p=0.005). Gly49 carrier status was associated with MACE (HR 1.62; 95% CI 1.00–2.68) and ischemic stroke (HR 1.81; 95% CI 1.01–3.23) in SPS3 and with small artery ischemic stroke (OR 1.14; 95% CI 1.03–1.26) in SiGN. In SPS3, β-blocker-treated Gly49 carriers had increased MACE versus non-β-blocker-treated individuals and non-carriers (HR 2.03; 95% CI 1.20–3.45). No associations were observed with the Arg389Gly polymorphism. Conclusion Among individuals with previous small artery ischemic stroke, the ADRB1 Gly49 polymorphism was associated with MACE, particularly small artery ischemic stroke, a risk that may be increased among β-blocker-treated individuals. Further research is needed to define β-blocker benefit among ischemic stroke patients by ADRB1 genotype. Clinical Trial Registration-URL http://www.clinicaltrials.gov. Unique identifier: NCT00059306.

We used electronic health records (EHR) data from 5,658 ambulatory chronic kidney disease (CKD) patients with hypertension and prescribed antihypertensive therapy to examine antihypertensive drug prescribing patterns, blood pressure (BP) control, and risk factors for resistant hypertension (RHTN) in a real-world setting. Two-thirds of CKD patients and three-fourths of those with proteinuria were prescribed guideline-recommended renoprotective agents including an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB); however, one-third were not prescribed an ACEI or ARB. CKD patients, particularly those with stages 1-2 CKD who were prescribed regimens including beta-blocker (BB)+diuretic or ACEI/ARB+BB+diuretic were more likely to have controlled BP (<140/90 mmHg) compared to those prescribed other combinations. Risk factors for RHTN included African American race and major comorbidities. Clinicians may use these findings to tailor antihypertensive therapy to the needs of each patient, including providing CKD stage-specific treatment, and better identify CKD patients at risk of RHTN.