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Exploring the utility of alcohol flushing as an instrumental variable for alcohol intake in Koreans.

ABSTRACT: Previous studies have indicated an association of higher alcohol intake with cardiovascular disease and related traits, but causation has not been definitively established. In this study, the causal effect of alcohol intake on hypertension in 2,011 men and women from the Ansan-Ansung cohort was estimated using an instrumental variable (IV) approach, with both a phenotypic and genotypic instrument for alcohol intake: alcohol flushing and the rs671 genotype (in the alcohol dehydrogenase 2 [ALDH2] gene), respectively. Both alcohol flushing and the rs671 genotype were associated with alcohol intake (difference in alcohol intake with alcohol flushers vs. non-flushers: -9.07?g/day; 95% confidence interval [CI]: -11.12, -7.02; P-value: 8.3?×?10-18 and with the rs671 GA?+?AA vs. GG genotype: -7.94?g/day; 95% CI: -10.20, -5.69; P-value: 6.1?×?10-12). An increase in alcohol intake, as predicted by both the absence of alcohol flushing and the presence of the rs671 GG genotype in the IV analyses, was associated with an increase in blood pressure in men from this Korean population. In conclusion, this study supports a causal effect of alcohol intake on hypertension and indicated that alcohol flushing may be a valid proxy for the ALDH2 rs671 polymorphism, which influences alcohol intake in this Korean population.

SUBMITTER: Cho Y

PROVIDER: S-EPMC5765011 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Exploring the utility of alcohol flushing as an instrumental variable for alcohol intake in Koreans.

Cho Yoonsu Y Kwak Soyoung S Lewis Sarah J SJ Wade Kaitlin H KH Relton Caroline L CL Smith George Davey GD Shin Min-Jeong MJ

Scientific reports 20180111 1

Previous studies have indicated an association of higher alcohol intake with cardiovascular disease and related traits, but causation has not been definitively established. In this study, the causal effect of alcohol intake on hypertension in 2,011 men and women from the Ansan-Ansung cohort was estimated using an instrumental variable (IV) approach, with both a phenotypic and genotypic instrument for alcohol intake: alcohol flushing and the rs671 genotype (in the alcohol dehydrogenase 2 [ALDH2] ...[more]

PMID: 29323248

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Project description:BackgroundThe developmental overnutrition hypothesis suggests that greater maternal obesity during pregnancy results in increased offspring adiposity in later life. If true, this would result in the obesity epidemic progressing across generations irrespective of environmental or genetic changes. It is therefore important to robustly test this hypothesis.Methods and findingsWe explored this hypothesis by comparing the associations of maternal and paternal pre-pregnancy body mass index (BMI) with offspring dual energy X-ray absorptiometry (DXA)-determined fat mass measured at 9 to 11 y (4,091 parent-offspring trios) and by using maternal FTO genotype, controlling for offspring FTO genotype, as an instrument for maternal adiposity. Both maternal and paternal BMI were positively associated with offspring fat mass, but the maternal association effect size was larger than that in the paternal association in all models: mean difference in offspring sex- and age-standardised fat mass z-score per 1 standard deviation BMI 0.24 (95% confidence interval [CI]: 0.22 to 0.26) for maternal BMI versus 0.13 (95% CI: 0.11, 0.15) for paternal BMI; p-value for difference in effect < 0.001. The stronger maternal association was robust to sensitivity analyses assuming levels of non-paternity up to 20%. When maternal FTO, controlling for offspring FTO, was used as an instrument for the effect of maternal adiposity, the mean difference in offspring fat mass z-score per 1 standard deviation maternal BMI was -0.08 (95% CI: -0.56 to 0.41), with no strong statistical evidence that this differed from the observational ordinary least squares analyses (p = 0.17).ConclusionsNeither our parental comparisons nor the use of FTO genotype as an instrumental variable, suggest that greater maternal BMI during offspring development has a marked effect on offspring fat mass at age 9-11 y. Developmental overnutrition related to greater maternal BMI is unlikely to have driven the recent obesity epidemic.

Project description:OBJECTIVES:To assess the incremental effects of adding extra antihypertensive drugs from a new class to a patient's regimen. DESIGN:Instrumental variable analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). To account for confounding by indication-when treatments seem less effective if they are administered to sicker patients-randomization status was used as the instrumental variable. Patients' randomization status was either intensive (systolic blood pressure target <120 mm Hg) or standard (systolic blood pressure target <140 mm Hg) treatment. Results from instrumental variable models were compared with those from standard multivariable models. SETTING:Secondary data analysis of a randomized clinical trial conducted at 102 sites in 2010-15. PARTICIPANTS:9092 SPRINT participants with hypertension and increased cardiovascular risk but no history of diabetes or stroke. MAIN OUTCOMES MEASURES:Systolic blood pressure, major cardiovascular events, and serious adverse events. RESULTS:In standard multivariable models not adjusted for confounding by indication, addition of an antihypertensive drug from a new class was associated with modestly lower systolic blood pressure (-1.3 mm Hg, 95% confidence interval -1.6 to -1.0) and no change in major cardiovascular events (absolute risk of events per 1000 patient years, 0.5, 95% confidence interval -1.5 to 2.3). In instrumental variable models, the addition of an antihypertensive drug from a new class led to clinically important reductions in systolic blood pressure (-14.4 mm Hg, -15.6 to -13.3) and fewer major cardiovascular events (absolute risk -6.2, -10.9 to -1.3). Incremental reductions in systolic blood pressure remained large and similar in magnitude for patients already taking drugs from zero, one, two, or three or more drug classes. This finding was consistent across all subgroups of patients. The addition of another antihypertensive drug class was not associated with adverse events in either standard or instrumental variable models. CONCLUSIONS:After adjustment for confounding by indication, the addition of a new antihypertensive drug class led to large reductions in systolic blood pressure and major cardiovascular events among patients at high risk for cardiovascular events but without diabetes. Effects on systolic blood pressure persisted across all levels of baseline drug use and all subgroups of patients.

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Exploring the utility of alcohol flushing as an instrumental variable for alcohol intake in Koreans.

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Exploring the utility of alcohol flushing as an instrumental variable for alcohol intake in Koreans.

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