Table 2.
Top SNPs in meta-analysis of difference test (pDiff<0.005) and cross-product (pinteract<0.005) interactions between SSB consumption and SNPs on HDL-C and TG concentrations in CHARGE consortium cohorts*
| SNP | Location (Hg19) | Alleles (E/A)† | Minor Allele Frequency | Model‡ | SSB Intake Category | n | Effect Size (SE)§ | P-value | Direction‖ | I2 | p # |
|---|---|---|---|---|---|---|---|---|---|---|---|
|
| |||||||||||
| HDL-C (mg/dl) | |||||||||||
|
| |||||||||||
| Difference Test | p Diff | ||||||||||
|
| |||||||||||
| rs35709627†† | 72999171 | A/G | 0.05 | Model 1 | <1 serving/month | 24,389 | −0.01 (0.04) | 0.86 | +−++−−+++?? | 23% | 1.98E-05** |
| >1 serving/day | 4,033 | 3.23 (0.77) | 2.94E-05 | +?+?+?+?+?? | 0% | ||||||
| Model 2 | <1 serving/month | 23,801 | 0.006 (0.04) | 0.86 | +−++−−+++?? | 30% | 0.0001 | ||||
| >1 serving/day | 3,955 | 2.72 (0.72) | 0.0002 | +?+?+?+?+?? | 0% | ||||||
|
| |||||||||||
| rs71556729†† | 72989516 | T/C | 0.05 | Model 1 | <1 serving/month | 23,974 | 0.02 (0.06) | 0.77 | +?++−+++−?? | 0% | 4.78E-05** |
| >1 serving/day | 3,359 | 4.47 (1.10) | 5.02E-05 | ??+?+?+?+?? | 0% | ||||||
| Model 2 | <1 serving/month | 22,835 | 0.01 (0.05) | 0.83 | +?++−+−?−?? | 0% | 0.0001 | ||||
| >1 serving/day | 3,299 | 3.89 (1.04) | 0.0002 | ??+?+?+?+?? | 0% | ||||||
|
| |||||||||||
| rs71556736 | 73034929 | T/C | 0.13 | Model 1 | <1 serving/month | 24,389 | −0.0005 (0.02) | 0.98 | +−+++−−++?− | 60% | 0.0003 |
| >1 serving/day | 4,033 | 1.65 (0.47) | 0.0004 | +?+?+?+?+?? | 0% | ||||||
| Model 2 | <1 serving/month | 23,801 | 0.007 (0.02) | 0.69 | +−++++−++?? | 67% | 0.002 | ||||
| >1 serving/day | 3,955 | 1.34 (0.43) | 0.002 | +?+?+?+?+?? | 0% | ||||||
|
| |||||||||||
| rs73137017 | 72974413 | G/A | 0.04 | Model 1 | <1 serving/month | 24,020 | −0.05 (0.06) | 0.46 | −+−−+−++−?? | 0% | 0.002 |
| >1 serving/day | 3,933 | −3.13 (0.99) | 0.002 | −?−?−?−?−?? | 0% | ||||||
| Model 2 | <1 serving/month | 23,437 | −0.008 (0.05) | 0.88 | ++−−+−++−?? | 0% | |||||
| >1 serving/day | 3,855 | −2.64 (0.91) | 0.004 | −?−?−?−?−?? | 0% | 0.003 | |||||
|
| |||||||||||
| Cross-Product Interaction Test | p interact | ||||||||||
|
| |||||||||||
| rs71556729 | 72989516 | T/C | 0.03 | Model 1 | - | 55,418 | 0.66 (0.21) | - | +++++?+−+−− | 0% | 0.001 |
| Model 2 | - | 53,394 | 0.68 (0.20) | - | ++−++?+++?− | 26% | 0.0007 | ||||
|
| |||||||||||
| rs79578725 | 73002455 | A/G | 0.05 | Model 1 | - | 53,662 | −0.51 (0.18) | - | +?−+−?−−−−− | 0% | 0.005 |
| Model 2 | - | 52,328 | −0.18 (0.17) | - | +?++−?−−−−− | 0% | 0.28 | ||||
|
| |||||||||||
| TG (ln-mg/dl) | |||||||||||
|
| |||||||||||
| Difference Test | p Diff | ||||||||||
|
| |||||||||||
| rs799157 | 73020301 | T/C | 0.05 | Model 1 | <1 serving/month | 23,974 | 0.02 (0.01) | 0.11 | +?++++−++?? | 59% | 0.005 |
| >1 serving/day | 4,033 | 0.11 (0.03) | 0.002 | +?+?+?+?+?? | 0% | ||||||
|
| |||||||||||
| Model 2 | <1 serving/month | 23,403 | 0.02 (0.01) | 0.17 | +?++−−?+? | 68% | 0.008 | ||||
| >1 serving/day | 3,955 | 0.09 (0.03) | 0.004 | +?+?++?+? | 0% | ||||||
|
| |||||||||||
| Cross-Product Interaction Test | p interact | ||||||||||
|
| |||||||||||
| rs55673514 | 73021456 | G/A | 0.04 | Model 1 | - | 57,977 | 0.02 (0.01) | - | −+++++++?++ | 17% | 0.04 |
| Model 2 | - | 56,578 | 0.02 (0.01) | - | −+++++++++? | 0% | 0.005 | ||||
Top signals represent suggestive interactions pDiff<0.005 or pinteract<0.005c
Alleles presented as effect (E)/alternative (A) alleles
Model 1 adjusted for age (years), sex (male/female), total energy intake (kcal/day) field center (CHS, FHS, YFS, Fenland, RS, MESA), and accounted for family or population structure where applicable (FHS, YFS, Fenland, NEO, MESA, WGHS, Raine Study, MESA); Model 2 adjusted for Model 1 covariates plus cohort-specific definition of education, smoking, physical activity, alcohol intake, and body mass index (kg/m2).
For the difference test, β (SE) represents the direction and magnitude of the difference in the outcome trait with each additional effect allele among categories of SSB consumption. For the cross-product interaction test, β (SE) represents the direction and magnitude of the difference in the outcome trait with each additional effect allele, per each increase in category of SSB intake (<1 serving/month, 1-4 servings/month, 1-2 servings/week, 3-7 servings/week, >1 serving/day).
Order of cohorts for regression coefficient directions: Framingham Heart Study, Young Finns Study, Fenland Study, Cardiovascular Health Study, Netherlands Epidemiology in Obesity Study, Rotterdam Study, Women’s Genome Health Study, Women’s Health Initiative, Atherosclerosis Risk in Communities Sutyd, The Raine Study, Multi-Ethnic Study of Atherosclerosis (+, positive effect size; -, negative effect size; ?, SNP not available in cohort).
P represents pDiff for the difference test for the highest and lowest category of SSB intake (<1 serving/month vs. >1 serving/day). P represents pinteract for the cross-product interaction regression coefficient of additive SSBxSNP categories.
Linkage disequilibrium (R2) between rs13240662 and rs71556729=0.55 in European ancestry groups of Phase 3 (Version 5) of the 1000 Genomes Project.
Indicates a statistically significant interaction based on Bonferonni-corrected pDiff or pinteract<0.0001
CHARGE, Cohorts for Heart and Aging Research in Genetic Epidemiology; HDL-C, high-density lipoprotein cholesterol concentrations; SE, standard error; SNP, single nucleotide polymorphism; SSB, sugar-sweetened beverages; TG, triglyceride concentrations.