29 research outputs found
Maternal Genetic Variation Accounts in Part for the Associations of Maternal Size during Pregnancy with Offspring Cardiometabolic Risk in Adulthood
<div><p>Background</p><p>Maternal pre-pregnancy body-mass index (ppBMI) and gestational weight gain (GWG) are associated with cardiometabolic risk (CMR) traits in the offspring. The extent to which maternal genetic variation accounts for these associations is unknown.</p><p>Methods/Results</p><p>In 1249 mother-offspring pairs recruited from the Jerusalem Perinatal Study, we used archival data to characterize ppBMI and GWG and follow-up data from offspring to assess CMR, including body mass index (BMI), waist circumference, glucose, insulin, blood pressure, and lipid levels, at an average age of 32. Maternal genetic risk scores (GRS) were created using a subset of SNPs most predictive of ppBMI, GWG, and each CMR trait, selected among 1384 single-nucleotide polymorphisms (SNPs) characterizing variation in 170 candidate genes potentially related to fetal development and/or metabolic risk. We fit linear regression models to examine the associations of ppBMI and GWG with CMR traits with and without adjustment for GRS. Compared to unadjusted models, the coefficient for the association of a one-standard-deviation (SD) difference in GWG and offspring BMI decreased by 41% (95%CI −81%, −11%) from 0.847 to 0.503 and the coefficient for a 1SD difference in GWG and WC decreased by 63% (95%CI −318%, −11%) from 1.196 to 0.443. For other traits, there were no statistically significant changes in the coefficients for GWG with adjustment for GRS. None of the associations of ppBMI with CMR traits were significantly altered by adjustment for GRS.</p><p>Conclusions</p><p>Maternal genetic variation may account in part for associations of GWG with offspring BMI and WC in young adults.</p></div
Characteristics at birth and age 32, stratified by offspring sex.
<p>Values are expressed as mean (SD) or percent.</p><p>*Diabetes, hypertension, heart disease, or pre-eclampsia.</p><p>**Includes self-report of moderate or vigorous physical activity lasting at least 20 minutes, 3 or more time a week.</p
Additional file 1: of Gene-diet interaction effects on BMI levels in the Singapore Chinese population
Table S1. SNP information and Meta-analysis between 78 SNPs and BMI level. Table S2. Interaction between SNPs and AHEI-2010 dietary score on BMI. Table S3. Interaction between SNPs and total calories on BMI. Table S4. Interaction between SNPs and %protein on BMI. Table S5. Interaction between SNPs and út on BMI. Table S6. Interaction between SNPs and %SFA on BMI. Table S7. Interaction between SNPs and %MUFA on BMI. Table S8. Interaction between SNPs and %PUFA on BMI. Table S9. Interaction between SNPs and Êrbohydrate on BMI. Table S10. Interaction between SNPs and %starch on BMI. Table S11. Interaction between SNPs and fiber on BMI. Table S12. Interaction between SNPs and cholesterol on BMI. Table S13. Interaction between GRS and dietary factors on BMI in individual datasets used in the study. (PDF 1521 kb
Estimated dosage of maternally- and paternally-derived minor allele indicators for heterozygous (Aa) mothers-offspring pairs.
<p>Estimated dosage of maternally- and paternally-derived minor allele indicators for heterozygous (Aa) mothers-offspring pairs.</p
Combined* maternally-derived effects of SNPs spanning the <i>APOB</i> locus on BMI.
<p>Forty two SNPs spanning the APOB genomic locus with their corresponding meta-analysis (z-based) p-values for the maternally-derived associations (as -log10 values) are plotted as a function of chromosomal position. Estimated recombination rates are plotted to reflect the local LD structure around the associated SNP (blue) and its correlated proxies (red:R<sup>2</sup>≥0.8; orange:0.5≥R<sup>2</sup>>0.8; yellow:0.2≥R<sup>2</sup>>0.5; white:R<sup>2</sup><0.2). Combined (Z-based) p-value for <i>APOB</i> SNP rs1367117 excluding JPS is 7.4x10<sup>-5</sup> (presented in figure). Corresponding p-value including JPS is 7.8x10<sup>-6</sup> (presented in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005573#pgen.1005573.t001" target="_blank">Table 1</a>). *Results used to generate the plot are based on genome-wide data available in FHS, FamHS and ERF (and not including JPS where data are not available).</p
Genes selected for examination of parent-of-origin effects in JPS.
<p>Genes selected for examination of parent-of-origin effects in JPS.</p
Parent-of-origin effects of <i>APOB</i> SNP rs1367117<sup>a</sup> on adiposity and glycemic traits.
<p>JPS, Jerusalem Perinatal Study; FHS, Framingham Heart Study; FamHS, Family Heart Study; ERF, Erasmus Rucphen Family</p><p><sup>a</sup> Minor allele frequency (MAF) of SNP rs1367117 across studies: JPS 0.2, FHS 0.31, FamHS 0.34 (imputed data, R<sup>2</sup> = 0.925), ERF 0.31.</p><p><sup>b</sup> Standard errors (SEs) were calculated directly in JPS; in the other studies SEs were estimated by converting p-values into a z-statistic and setting: SE = beta/z.</p><p>Parent-of-origin effects of <i>APOB</i> SNP rs1367117<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005573#t001fn002" target="_blank"><sup>a</sup></a> on adiposity and glycemic traits.</p
Genotype effect of APOB SNP rs1367117 on cardio-metabolic traits.
<p>JPS, Jerusalem Perinatal Study; FHS, Framingham Heart Study; FamHS, Family Heart Study; ERF, Erasmus Rucphen Family</p><p><sup>a</sup> Based on an additive genetic model.</p><p><sup>b</sup> Numbers of probands included in the genotype effect analysis are larger compared to the POE analysis due to exclusion of individuals who were non-informative for parental transmission.</p><p>Genotype effect of APOB SNP rs1367117 on cardio-metabolic traits.</p
Maternally-derived effects of <i>APOB</i> SNP rs1367117 on cardio-metabolic traits with and without adjustment for BMI<sup>a</sup>.
<p>JPS, Jerusalem Perinatal Study; FHS, Framingham Heart Study; FamHS, Family Heart Study; ERF, Erasmus Rucphen Family</p><p><sup>a</sup> Presented betas and standard errors (SEs) are based on models without adjustment for BMI. P-values are presented for models with and without further adjustment for BMI. Beta and standard errors for BMI-adjusted models as well as for paternally-derived effects are provided in <a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005573#pgen.1005573.s008" target="_blank">S7 Table</a>.</p><p><sup>b</sup> Standard errors (SEs) were calculated directly in JPS; in the other studies SEs were estimated by converting p-values into a z-statistic and setting: SE = beta/z.</p><p>Maternally-derived effects of <i>APOB</i> SNP rs1367117 on cardio-metabolic traits with and without adjustment for BMI<a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1005573#t002fn002" target="_blank"><sup>a</sup></a>.</p
Indicators of parental origin of the minor allele in JPS.
<p>Indicators of parental origin of the minor allele in JPS.</p