Relationship of Alcohol Consumption and Type of Alcoholic Beverage Consumed With Plasma Lipid Levels: Differences Between Whites and African Americans of the ARIC Study

Background: Alcohol intake influences plasma lipid levels, and such effects may be moderated by genetic variants. We aimed to characterize the role of aggregated rare and low-frequency protein-coding variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. Methods: In the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, fasting plasma triglycerides and high- and low-density lipoprotein cholesterol were measured in 34 153 individuals with European ancestry from 5 discovery studies and 32 277 individuals from 6 replication studies. Rare and low-frequency functional protein-coding variants (minor allele frequency, ≤5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction test and a joint test of genetic main and gene-environment interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least 2 drinks per week, were considered. Results: We discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci ( PCSK9 , LPA , LPL , LIPG , ANGPTL4 , APOB , APOC3 , and CD300LG ) remained significant after conditioning on the common index single-nucleotide polymorphism identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on triglycerides in a novel locus was significantly discovered ( P =6.65×10 −6 for the interaction test) and replicated at nominal significance level ( P =0.013) in SMC5 . Conclusions: In conclusion, this study applied new gene-based statistical approaches and suggested that rare and low-frequency genetic variants interacted with alcohol consumption on lipid levels.

Download Full-text

Relationship of Asteroid Hyalosis to Diabetes Mellitus and Plasma Lipid Levels

American Journal of Ophthalmology ◽

10.1016/0002-9394(69)92056-x ◽

1969 ◽

Vol 67 (3) ◽

pp. 406-413 ◽

Cited By ~ 23

Author(s):

Malcolm Luxenberg ◽

David Sime

Keyword(s):

Diabetes Mellitus ◽

Plasma Lipid ◽

Lipid Levels ◽

Asteroid Hyalosis ◽

Relationship Of

Download Full-text

Role of Rare and Low Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

10.1101/561225 ◽

2019 ◽

Author(s):

Zhe Wang ◽

Han Chen ◽

Traci M. Bartz ◽

Lawrence F. Bielak ◽

Daniel I. Chasman ◽

...

Keyword(s):

Alcohol Consumption ◽

Association Studies ◽

Plasma Lipid ◽

Low Frequency ◽

Environment Interaction ◽

Genome Wide Association Studies ◽

Lipid Levels ◽

Gxe Interaction ◽

Fasting Plasma

AbstractBackgroundAlcohol intake influences plasma lipid levels and such effects may be modulated by genetic variants.ObjectiveWe aimed to characterize the role of aggregated rare and low-frequency variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels.DesignIn the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, fasting plasma triglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-c and LDL-c) were measured in 34,153 European Americans from five discovery studies and 32,275 individuals from six replication studies. Rare and low-frequency protein coding variants (minor allele frequency ≤ 5%) measured by an exome array were aggregated by genes and evaluated by a gene-environment interaction (GxE) test and a joint test of genetic main and GxE interaction effects. Two dichotomous self-reported alcohol consumption variables, current drinker, defined as any recurrent drinking behavior, and regular drinker, defined as the subset of current drinkers who consume at least two drinks per week, were considered.ResultsWe discovered and replicated 21 gene-lipid associations at 13 known lipid loci through the joint test. Eight loci (PCSK9, LPA, LPL, LIPG, ANGPTL4, APOB, APOC3 and CD300LG) remained significant after conditioning on the common index single nucleotide polymorphism (SNP) identified by previous genome-wide association studies, suggesting an independent role for rare and low-frequency variants at these loci. One significant gene-alcohol interaction on TG was discovered at a Bonferroni corrected significance level (p-value <5×10−5) and replicated (p-value <0.013 for the interaction test) inSMC5.ConclusionsIn conclusion, this study applied new gene-based statistical approaches to uncover the role of rare and low-frequency variants in gene-alcohol consumption interactions on lipid levels.

Download Full-text

Sex Hormone-Binding Globulin Is Associated with Obesity and Dyslipidemia in Prepubertal Children

Children ◽

10.3390/children7120272 ◽

2020 ◽

Vol 7 (12) ◽

pp. 272

Author(s):

Gihong Park ◽

Kyungchul Song ◽

Youngha Choi ◽

Jun Suk Oh ◽

Han Saem Choi ◽

...

Keyword(s):

Plasma Lipid ◽

Density Lipoprotein ◽

Sex Hormone ◽

Sex Hormone Binding Globulin ◽

Atherogenic Index ◽

Hormone Binding ◽

Lipid Levels ◽

Prepubertal Children ◽

Overweight Group ◽

Relationship Of

Sex hormone-binding globulin (SHBG) is associated with age, sex, and puberty. The association of SHBG with various diseases has been suggested nowadays, however, the relationships in prepubertal children have not been sufficiently investigated. This study analyzed the relationship of SHBG with body mass index (BMI) and plasma lipid levels in prepubertal children. We evaluated the association of SHBG with BMI among the 693 prepubertal children subdivided into normal, overweight, and obese groups, with plasma lipid levels among the children subdivided into normal and dyslipidemia groups. The obese and overweight group had lower SHBG levels than the normal BMI group in both sexes. The dyslipidemia group included subjects with low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TG), or a high atherogenic index of plasma (AIP); this group had lower SHBG than the normal lipid group. SHBG was positively correlated with HDL-C, and negatively correlated with TG and AIP. After adjusting for BMI, SHBG was positively correlated with HDL-C and negatively correlated with TG and AIP in all groups. In conclusion, SHBG levels are closely correlated with BMI in prepubertal children. SHBG may play a meaningful role in the decrease in HDL-C and increase in TG during prepubertal age.

Download Full-text

Cigarette Smoking, Alcohol Consumption, and Risk of Systemic Lupus Erythematosus: A Case-control Study in a Japanese Population

The Journal of Rheumatology ◽

10.3899/jrheum.111609 ◽

2012 ◽

Vol 39 (7) ◽

pp. 1363-1370 ◽

Cited By ~ 33

Author(s):

CHIKAKO KIYOHARA ◽

MASAKAZU WASHIO ◽

TAKAHIKO HORIUCHI ◽

TOYOKO ASAMI ◽

SABURO IDE ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Alcohol Consumption ◽

Cigarette Smoking ◽

Lupus Erythematosus ◽

Alcoholic Beverage ◽

Alcoholic Beverages ◽

Moderate Alcohol Consumption ◽

Systemic Lupus ◽

Increased Risk ◽

Relationship Of

Objective.Cigarette smoking may be associated with increased risk of systemic lupus erythematosus (SLE), whereas the role of alcohol consumption is unknown. We examined the association between SLE risk and smoking or drinking.Methods.We investigated the relationship of smoking and drinking compared to SLE risk among 171 SLE cases and 492 healthy controls in female Japanese subjects. Unconditional logistic regression was used to compute OR and 95% CI, with adjustments for several covariates.Results.Compared with nonsmoking, current smoking was significantly associated with increased risk of SLE (OR 3.06, 95% CI 1.86–5.03). The higher the level of exposure to cigarette smoke, the higher the risk of SLE. Inhalation was also associated with increased SLE risk (OR 3.73, 95% CI 1.46–9.94 for moderate inhalation; OR 3.06, 95% CI 1.81–5.15 for deep inhalation). In contrast, light/moderate alcohol consumption had a protective effect on SLE risk (OR 0.38, 95% CI 0.19–0.76). As for beer, the risks for non-beer drinkers and beer drinkers were similar. This also applies to alcoholic beverages other than beer.Conclusion.Our results suggest that smoking was positively associated with increased SLE risk whereas light/moderate alcohol consumption was inversely associated with SLE risk, irrespective of the type of alcoholic beverage. Additional studies are warranted to confirm these findings.

Download Full-text

Abstract MP62: Role of Rare and Low-Frequency Variants in Gene-Alcohol Interactions on Plasma Lipid Levels

Circulation ◽

10.1161/circ.137.suppl_1.mp62 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Zhe Wang ◽

Han Chen ◽

Daniel I Chasman ◽

Ching-Ti Liu ◽

Raymond Noordam ◽

...

Keyword(s):

Alcohol Consumption ◽

Plasma Lipid ◽

Low Frequency ◽

Joint Analysis ◽

Genome Wide Association Studies ◽

Lipid Levels ◽

Gxe Interaction ◽

Functional Variants ◽

Fasting Plasma

Introduction: Alcohol intake modifies plasma lipid levels and such effects may be modulated by genetic variants. We use emerging statistical methods that extend well-established common variant approaches to characterize the role of aggregated rare and low-frequency variants in gene by alcohol consumption interactions associated with fasting plasma lipid levels. Methods: Up to 247,870 exonic variants on the Illumina HumanExome BeadChip and fasting plasma triglycerides (TG), and high- and low-density lipoprotein cholesterol (HDL-c and LDL-c) were measured in 46,443 European Americans from 4 studies (the Atherosclerosis Risk in Communities (ARIC) study, the Framingham Heart Study, the Netherlands Epidemiology of Obesity Study and the Women’s Genome Health Study) of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Using the gene-based rareGE method, we conducted exome-wide gene-environment (GxE) tests with genetic main effects estimated as fixed and random effects, and a joint analysis of genetic main and GxE interaction effects. Rare and low-frequency (minor allele frequency ≤ 5%) functional variants, (i.e. frameshift, nonsynonymous, stop/gain, stop/loss, and splicing) were aggregated by genes. Two dichotomous self-reported alcohol consumption variables, current drinker (at least 1 drink per week, yes/no) and regular drinker (at least 2 drinks per week, yes/no) were considered. A sample size weighted Z-test (weighted Stouffer’s method) was used to meta-analyze study-specific p -values. Exome-wide significance level was set at p < 3.7*10 -6 (0.05/13368 genes), using a Bonferroni procedure to correct for multiple testing. Results: We identified 24 gene-lipid associations at 13 known lipid loci (within 500kb) harboring rare and low-frequency variants through the joint analysis. In ARIC, numerous genes ( PCSK9, LPL, LIPG, ANGPTL4, APOB, APOC3-A5 ) remained significant after conditioning on common index single nucleotide polymorphisms (SNPs), suggesting an independent role for rare variants at loci highlighted by previous genome-wide association studies. However, no significant gene-alcohol interactions were observed with rare and low-frequency variants on TG, HDL-c or LDL-c. Conclusion: This study applied new statistical approaches to investigate the role of rare and low-frequency variants in gene-alcohol consumption interactions on lipid levels. Results show promise for other larger scale studies analyzing rare variant GxE interactions.

Download Full-text