The genetic association between blood pressure (BP) at rest and during the cold pressor test (CPT) is not well characterized. The purpose of this study was to examine the genetic architecture of BP during the CPT, and to determine whether BP at rest and during the CPT share common genetic influences. In 419 individuals distributed across four large families, variance components methods were used to estimate heritabilities of resting BP and CPT BP, along with genetic correlations among BP traits. The CPT consisted of immersion of the left foot in 4°C water while the participant was supine. Blood pressure reactivity (ΔBP) was defined as BP at 15 to 30 sec and 45 to 60 sec of foot immersion minus resting BP. Significant (P < .05) heritabilities were found for supine BP (h²_SBP = 0.35), CPT BP (h²_SBP = 0.27 and 0.33, h²_DBP = 0.18 and 0.30), and ΔSBP (h²_SBP = 0.12 and 0.37) but not for ΔDBP. Bivariate analyses detected significant (P < .05) genetic correlations between resting SBP and CPT SBP that were different from 0 and 1. Genetic correlations between resting DBP and CPT DBP were not significantly different from 1. Genetic correlations between resting SBP andΔSBP were not significant. Measures of BP at rest and during cold immersion are significantly influenced by additive genetic effects. These genetic influences are only partially shared between SBP at rest and SBP during cold immersion, suggesting that a somewhat different set of genes may influence SBP during cold immersion. Unique sets of genes also appear to influence ΔSBP independent of those influencing resting SBP. Am J Hypertens 2005;18:1211–1217 © 2005 American Journal of Hypertension, Ltd.

The genetic influences on bone mass likely change throughout the life span, but most genetic studies of bone mass regulation have focused on adults. There is, however, a growing awareness of the importance of genes influencing the acquisition of bone mass during childhood on lifelong bone health. The present investigation examines genetic influences on childhood bone mass by estimating the residual heritabilities of different measures of second metacarpal bone mass in a sample of 600 10-year-old participants from 144 families in the Fels Longitudinal Study. Bivariate quantitative genetic analyses were conducted to estimate genetic correlations between cortical bone mass measures, and measures of bone growth and development. Using a maximum likelihood-based variance components method for pedigree data, we found a residual heritability estimate of 0.71 for second metacarpal cortical index. Residual heritability estimates for individual measures of cortical bone (e.g., lateral cortical thickness, medial cortical thickness) ranged from 0.47 to 0.58, at this pre-pubertal childhood age. Low genetic correlations were found between cortical bone measures and both bone length and skeletal age. However, after Bonferonni adjustment for multiple testing, rho(G) was not significantly different from 0 for any of these pairs of traits. Results of this investigation provide evidence of significant genetic control over bone mass largely independent of maturation while bones are actively growing and before rapid accrual of bone that typically occurs during puberty.

The identification of causal genomic regions for liver fat accumulation in the context of metabolic dysfunction remains a challenging goal. This study aimed to identify potential endophenotypes for liver fat content and employ them in bivariate linkage searches for pleiotropic genetic regions where targeted association analysis is more likely to reveal significant variants. Multiple metabolic risk and adiposity distribution traits were assessed using the endophenotype ranking value. The top-ranked endophenotypes were then used in a bivariate linkage analysis, paired with liver fat content. Quantitative trait loci (QTLs) identified as significant or suggestive were targeted for measured genotype association analyses. The highest-ranked endophenotypes for liver fat accumulation were insulin resistance (IR), visceral adipose tissue (VAT), and high-density lipoprotein cholesterol (HDL-C). The univariate linkage analysis for liver fat content identified one significant QTL at chromosome 17p13.2 (Logarithm of odds score (LOD) = 2.90, p = 1.29 × 10⁻⁴). The bivariate linkage analysis pairing liver fat with IR and VAT improved the localization of two suggestive QTLs at 13q21.31 (LOD = 2.11, p = 9.03 × 10⁻⁴), and 6q21 (LOD = 2.35, p = 5.07 × 10⁻⁴), respectively. Targeted association analyses within the -1-LOD score regions of these QTLs revealed 17 marginally significant single nucleotide polymorphisms (SNPs) associated with liver fat content or its combination with the selected endophenotypes. The endophenotype-informed linkage analysis successfully identified regions suitable for the targeted association analysis of liver fat content, either alone or in combination with IR or VAT, leading to the discovery of marginally significant variants with potential for future functional studies.