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Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9.

Simino J, Sung YJ, Kume R, Schwander K, Rao DC - Front Genet (2013)

Bottom Line: We then calculated the joint 2 df score test of the SNP main effect and SNP-alcohol interaction using MixABEL.The effect of SNP rs10826334 (near SLC16A9) on SBP was significantly modulated by both the number of alcoholic drinks and the ounces of alcohol consumed per week (p-values of 1.27E-08 and 3.92E-08, respectively).SNP-alcohol interactions may enhance discovery of novel variants with large effects that can be targeted with lifestyle modifications.

View Article: PubMed Central - PubMed

Affiliation: Division of Biostatistics, Washington University School of Medicine St. Louis, MO, USA.

ABSTRACT
Alcohol consumption is a known risk factor for hypertension, with recent candidate studies implicating gene-alcohol interactions in blood pressure (BP) regulation. We used 6882 (predominantly) Caucasian participants aged 20-80 years from the Framingham SNP Health Association Resource (SHARe) to perform a genome-wide analysis of SNP-alcohol interactions on BP traits. We used a two-step approach in the ABEL suite to examine genetic interactions with three alcohol measures (ounces of alcohol consumed per week, drinks consumed per week, and the number of days drinking alcohol per week) on four BP traits [systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure]. In the first step, we fit a linear mixed model of each BP trait onto age, sex, BMI, and antihypertensive medication while accounting for the phenotypic correlation among relatives. In the second step, we conducted 1 degree-of-freedom (df) score tests of the SNP main effect, alcohol main effect, and SNP-alcohol interaction using the maximum likelihood estimates (MLE) of the parameters from the first step. We then calculated the joint 2 df score test of the SNP main effect and SNP-alcohol interaction using MixABEL. The effect of SNP rs10826334 (near SLC16A9) on SBP was significantly modulated by both the number of alcoholic drinks and the ounces of alcohol consumed per week (p-values of 1.27E-08 and 3.92E-08, respectively). Each copy of the G-allele decreased SBP by 3.79 mmHg in those consuming 14 drinks per week vs. a 0.461 mmHg decrease in non-drinkers. Index SNPs in 20 other loci exhibited suggestive (p-value ≤ 1E-06) associations with BP traits by the 1 df interaction test or joint 2 df test, including 3 rare variants, one low-frequency variant, and SNPs near/in genes ESRRG, FAM179A, CRIPT-SOCS5, KAT2B, ADCY2, GLI3, ZNF716, SLIT1, PDE3A, KERA-LUM, RNF219-AS1, CLEC3A, FBXO15, and IGSF5. SNP-alcohol interactions may enhance discovery of novel variants with large effects that can be targeted with lifestyle modifications.

No MeSH data available.


Related in: MedlinePlus

Manhattan plots of the joint 2 degree-of-freedom test of the SNP main effect and SNP-drinks per week interaction for each blood pressure trait. The -log(p-value) of the joint 2 df test of each SNP was plotted vs. the chromosomal location for all SNPs genome-wide. Sixteen unique loci were discovered using the four blood pressure traits.
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Figure 1: Manhattan plots of the joint 2 degree-of-freedom test of the SNP main effect and SNP-drinks per week interaction for each blood pressure trait. The -log(p-value) of the joint 2 df test of each SNP was plotted vs. the chromosomal location for all SNPs genome-wide. Sixteen unique loci were discovered using the four blood pressure traits.

Mentions: Our genome-wide analysis of SNP × alcohol interactions yielded one significant (p ≤ 5E-08) and 20 suggestive (p ≤ 1E-06) BP loci (using either the 1 or 2 df test of SNP-alcohol interactions). The number of loci associated with SBP, DBP, MAP, and PP were 8, 4, 9, and 3, respectively; three loci were associated with more than one trait. The alcohol measure with the largest sample size, drinks of alcohol per week, enabled the discovery of 16 of the 21 loci. The Manhattan plots in Figure 1 display the genome-wide results for the joint 2 df test of the SNP main effect and SNP-drinks per week interaction on all 4 BP traits. Six loci achieved significant or suggestive associations for BP traits in the ounces of alcohol consumed per week interaction analysis, while only 3 loci reached suggestive association in the number of days drinking per week interaction analysis.


Gene-alcohol interactions identify several novel blood pressure loci including a promising locus near SLC16A9.

Simino J, Sung YJ, Kume R, Schwander K, Rao DC - Front Genet (2013)

Manhattan plots of the joint 2 degree-of-freedom test of the SNP main effect and SNP-drinks per week interaction for each blood pressure trait. The -log(p-value) of the joint 2 df test of each SNP was plotted vs. the chromosomal location for all SNPs genome-wide. Sixteen unique loci were discovered using the four blood pressure traits.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860258&req=5

Figure 1: Manhattan plots of the joint 2 degree-of-freedom test of the SNP main effect and SNP-drinks per week interaction for each blood pressure trait. The -log(p-value) of the joint 2 df test of each SNP was plotted vs. the chromosomal location for all SNPs genome-wide. Sixteen unique loci were discovered using the four blood pressure traits.
Mentions: Our genome-wide analysis of SNP × alcohol interactions yielded one significant (p ≤ 5E-08) and 20 suggestive (p ≤ 1E-06) BP loci (using either the 1 or 2 df test of SNP-alcohol interactions). The number of loci associated with SBP, DBP, MAP, and PP were 8, 4, 9, and 3, respectively; three loci were associated with more than one trait. The alcohol measure with the largest sample size, drinks of alcohol per week, enabled the discovery of 16 of the 21 loci. The Manhattan plots in Figure 1 display the genome-wide results for the joint 2 df test of the SNP main effect and SNP-drinks per week interaction on all 4 BP traits. Six loci achieved significant or suggestive associations for BP traits in the ounces of alcohol consumed per week interaction analysis, while only 3 loci reached suggestive association in the number of days drinking per week interaction analysis.

Bottom Line: We then calculated the joint 2 df score test of the SNP main effect and SNP-alcohol interaction using MixABEL.The effect of SNP rs10826334 (near SLC16A9) on SBP was significantly modulated by both the number of alcoholic drinks and the ounces of alcohol consumed per week (p-values of 1.27E-08 and 3.92E-08, respectively).SNP-alcohol interactions may enhance discovery of novel variants with large effects that can be targeted with lifestyle modifications.

View Article: PubMed Central - PubMed

Affiliation: Division of Biostatistics, Washington University School of Medicine St. Louis, MO, USA.

ABSTRACT
Alcohol consumption is a known risk factor for hypertension, with recent candidate studies implicating gene-alcohol interactions in blood pressure (BP) regulation. We used 6882 (predominantly) Caucasian participants aged 20-80 years from the Framingham SNP Health Association Resource (SHARe) to perform a genome-wide analysis of SNP-alcohol interactions on BP traits. We used a two-step approach in the ABEL suite to examine genetic interactions with three alcohol measures (ounces of alcohol consumed per week, drinks consumed per week, and the number of days drinking alcohol per week) on four BP traits [systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure]. In the first step, we fit a linear mixed model of each BP trait onto age, sex, BMI, and antihypertensive medication while accounting for the phenotypic correlation among relatives. In the second step, we conducted 1 degree-of-freedom (df) score tests of the SNP main effect, alcohol main effect, and SNP-alcohol interaction using the maximum likelihood estimates (MLE) of the parameters from the first step. We then calculated the joint 2 df score test of the SNP main effect and SNP-alcohol interaction using MixABEL. The effect of SNP rs10826334 (near SLC16A9) on SBP was significantly modulated by both the number of alcoholic drinks and the ounces of alcohol consumed per week (p-values of 1.27E-08 and 3.92E-08, respectively). Each copy of the G-allele decreased SBP by 3.79 mmHg in those consuming 14 drinks per week vs. a 0.461 mmHg decrease in non-drinkers. Index SNPs in 20 other loci exhibited suggestive (p-value ≤ 1E-06) associations with BP traits by the 1 df interaction test or joint 2 df test, including 3 rare variants, one low-frequency variant, and SNPs near/in genes ESRRG, FAM179A, CRIPT-SOCS5, KAT2B, ADCY2, GLI3, ZNF716, SLIT1, PDE3A, KERA-LUM, RNF219-AS1, CLEC3A, FBXO15, and IGSF5. SNP-alcohol interactions may enhance discovery of novel variants with large effects that can be targeted with lifestyle modifications.

No MeSH data available.


Related in: MedlinePlus