Search

Significant relations were observed between select infant-care and weaning behaviors and growth in body weight in common marmoset monkeys (Callithrix jacchus). The patterns of these relations suggest that earlier occurrence of developmental milestones, such as cessation of transport (being off carriers) and weaning to solid food, were associated with slower growth during the subsequent period. In contrast, more frequent nursing bouts during the period in which weaning was initiated were associated with higher growth rates. In the case of being off carriers, these effects did not carry over to older ages, suggesting that any deficits in growth were temporary. In the case of earlier, more frequent consumption of solid food, there was some suggestion that there were longer-term effects, followed by catch-up growth. The knee-to-heel length of subjects was not related to the measured behaviors. There was no relation between early weaning to solid food and leanness at day 75, suggesting that, although this behavior was affecting overall weight, it did not affect relative gains of fat versus lean mass. There were, however, significant correlations between cessation of transport or frequency of nursing bouts during the weaning period and leanness, with earlier cessation of transport and less frequent nursing associated with leaner infants, after weaning. Our results differed from those of a previous study that found a relation between linear growth and abuse in this species, with abuse defined as physical injury by other members of the group. We found no differences in growth between abused and nonabused infants. However, abused infants had lower birth weight.

Significant relations were observed between select infant-care and weaning behaviors and growth in body weight in common marmoset monkeys (Callithrix jacchus). The patterns of these relations suggest that earlier occurrence of developmental milestones, such as cessation of transport (being off carriers) and weaning to solid food, were associated with slower growth during the subsequent period. In contrast, more frequent nursing bouts during the period in which weaning was initiated were associated with higher growth rates. In the case of being off carriers, these effects did not carry over to older ages, suggesting that any deficits in growth were temporary. In the case of earlier, more frequent consumption of solid food, there was some suggestion that there were longer-term effects, followed by catch-up growth. The knee-to-heel length of subjects was not related to the measured behaviors. There was no relation between early weaning to solid food and leanness at day 75, suggesting that, although this behavior was affecting overall weight, it did not affect relative gains of fat versus lean mass. There were, however, significant correlations between cessation of transport or frequency of nursing bouts during the weaning period and leanness, with earlier cessation of transport and less frequent nursing associated with leaner infants, after weaning. Our results differed from those of a previous study that found a relation between linear growth and abuse in this species, with abuse defined as physical injury by other members of the group. We found no differences in growth between abused and nonabused infants. However, abused infants had lower birth weight.

Abstract The Framingham Heart Study, founded in 1948 to examine the epidemiology of cardiovascular disease in a small town outside of Boston, has become the worldwide standard for cardiovascular epidemiology. It is among the longest running, most comprehensively characterized multi-generational studies in the world. Such seminal findings as the effects of smoking and high cholesterol on heart disease came from the Framingham Heart Study. At the time of publication these were novel cardiovascular disease (CVD) risk factors, now they are the basis of treatment and prevention in the US. Is the Framingham study now on it's way to becoming the gold standard for genetic epidemiology of CVD? Will the novel genetic findings of today become the health care standards of tomorrow? The accompanying articles summarizing the results of genome-wide association studies (GWAS) give the reader a first glimpse into the possibilities.

Abstract Background Previously, we reported significant linkage of body mass index (BMI) to chromosomes 6 and 11 across six examinations, covering 28 years, of the Framingham Heart Study. These results were on all individuals available at each exam, thus the sample size varied from exam to exam. To remove any effect of sample size variation we have now constructed six subsets; for each exam individuals were only included if they were measured at every exam, i.e. for each exam, included individuals comprise the intersection of the original six exams. This strategy preferentially removed older individuals who died before reaching the sixth exam, thus the intersection datasets are smaller (n = 1114) and significantly younger than the full datasets. We performed variance components linkage analysis on these intersection datasets and on their sex-specific subsets. Results Results from the sex-specific genome scans revealed 11 regions in which a sex-specific maximum lodscore was at least 2.0 for at least one dataset. Randomization tests indicated that all 11 regions had significant (p < 0.05) differences in sex-specific maximum lodscores for at least three datasets. The strongest sex-specific linkage was for men on chromosome 16 with maximum lodscores 2.70, 3.00, 3.42, 3.61, 2.56 and 1.93 for datasets 1–6 respectively. Results from the full genome scans revealed that linked regions on chromosomes 6 and 11 remained significantly and consistently linked in the intersection datasets. Surprisingly, the maximum lodscore on chromosome 10 for dataset 1 increased from 0.97 in the older original dataset to 4.23 in the younger smaller intersection dataset. This difference in maximum lodscores was highly significant (p < 0.0001), implying that the effect of this chromosome may vary with age. Age effects may also exist for the linked regions on chromosomes 6 and 11. Conclusion Sex specific effects of chromosomal regions on BMI are common in the Framingham study. Some evidence also exists for age-specific effects of chromosomal regions.

Exposure of biological systems to acute or chronic insults triggers a host of molecular and physiological responses to either tolerate, adapt, or fully restore homeostasis; these responses constitute the hallmarks of resilience. Given the many facets, dimensions, and discipline-specific focus, gaining a shared understanding of "resilience" has been identified as a priority for supporting advances in cardiovascular health. This report is based on the working definition: "Resilience is the ability of living systems to successfully maintain or return to homeostasis in response to physical, molecular, individual, social, societal, or environmental stressors or challenges," developed after considering many factors contributing to cardiovascular resilience through deliberations of multidisciplinary experts convened by the National Heart, Lung, and Blood Institute during a workshop entitled: "Enhancing Resilience for Cardiovascular Health and Wellness." Some of the main emerging themes that support the possibility of enhancing resilience for cardiovascular health include optimal energy management and substrate diversity, a robust immune system that safeguards tissue homeostasis, and social and community support. The report also highlights existing research challenges, along with immediate and long-term opportunities for resilience research. Certain immediate opportunities identified are based on leveraging existing high-dimensional data from longitudinal clinical studies to identify vascular resilience measures, create a 'resilience index,' and adopt a life-course approach. Long-term opportunities include developing quantitative cell/organ/system/community models to identify resilience factors and mechanisms at these various levels, designing experimental and clinical interventions that specifically assess resilience, adopting global sharing of resilience-related data, and cross-domain training of next-generation researchers in this field., (© 2022 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Background and Objectives: Adult class II/III obesity (BMI ≥ 35 kg/m 2 ) has significant adverse health outcomes. Early prevention and treatment are critical, but prospective childhood risk estimates are lacking. This study aimed to define the prospective risk of adult class II/III obesity, using childhood BMI., Methods: Children ages 3-19 years enrolled in cohorts of the International Childhood Cardiovascular Cohort (i3C) consortium with measured BMI assessments in childhood and adulthood were included. Prospective risk of adult class II/III obesity was modeled based on childhood age, sex, race, and BMI., Results: A total of 12,142 individuals (44% male, 85% white) were assessed at median age 14 [Interquartile range, IQR: 11, 16] and 33 [28, 39] years. Class II/III adult obesity developed in 6% of children with normal weight; 29% of children with overweight; 56% of children with obesity; and 80% of children with severe obesity. However, 38% of the 1440 adults with class II/III obesity (553/1440) were normal weight as children. Prospective risk of adult class II/III obesity varied by age, sex, and race within childhood weight status classifications, and is notably higher for girls, black participants, and those in the United States. The risk of class II/III obesity increased with older adult age., Conclusions: Children with obesity or severe obesity have a substantial risk of adult class II/III obesity, and observed prospective risk estimates are now presented by age, sex, race, and childhood BMI. Clinical monitoring of children's BMI for adult class II/III obesity risk may be especially important for females and black Americans.

Cardiovascular diseases remain the leading cause of mortality and a major contributor to preventable deaths worldwide. The dominant modifiable risk factors and the social and environmental determinants that increase cardiovascular risk are known, and collectively, are as important in racial and ethnic minority populations as they are in majority populations. Their prevention and treatment remain the foundation for cardiovascular health promotion and disease prevention. Genetic and epigenetic factors are increasingly recognized as important contributors to cardiovascular risk and provide an opportunity for advancing precision cardiovascular medicine. In this review, we explore emerging concepts at the interface of precision medicine and cardiovascular disease in racial and ethnic minority populations. Important among these are the lack of racial and ethnic diversity in genomics studies and biorepositories; the resulting misclassification of benign variants as pathogenic in minorities; and the importance of ensuring ancestry-matched controls in variant interpretation. We address the relevance of epigenetics, pharmacogenomics, genetic testing and counseling, and their social and cultural implications. We also examine the potential impact of precision medicine on racial and ethnic disparities. The National Institutes of Health's All of Us Research Program and the National Heart, Lung, and Blood Institute's Trans-Omics for Precision Medicine Initiative are presented as examples of research programs at the forefront of precision medicine and diversity to explore research implications in minorities. We conclude with an overview of implementation research challenges in precision medicine and the ethical implications in minority populations. Successful implementation of precision medicine in cardiovascular disease in minority populations will benefit from strategies that directly address diversity and inclusion in genomics research and go beyond race and ethnicity to explore ancestry-matched controls, as well as geographic, cultural, social, and environmental determinants of health.

Although it is widely thought that childhood levels of cardiovascular (CV) risk factors are related to adult CV disease, longitudinal data directly linking the two are lacking. This paper describes the design and organization of the International Childhood Cardiovascular Cohort Consortium Outcomes Study (i3C Outcomes), the first longitudinal cohort study designed to locate adults with detailed, repeated, childhood biological, physical, and socioeconomic measurements and a harmonized database. I3C Outcomes uses a Heart Health Survey (HHS) to obtain information on adult CV endpoints, using mail, email, telephone, and clinic visits in the United States (U.S.) and Australia and a national health database in Finland. Microsoft Access, REsearch Data Capture (REDCap) (U.S.), LimeSurvey (Australia), and Medidata™ Rave data systems are used to collect, transfer and organize data. Self-reported CV events are adjudicated via hospital and doctor-released medical records. After the first two study years, participants (N = 10,968) were more likely to be female (56% vs. 48%), non-Hispanic white (90% vs. 80%), and older (10.4 ± 3.8 years vs. 9.4 ± 3.3 years) at their initial childhood study visit than the currently non-recruited cohort members. Over 48% of cohort members seen during both adulthood and childhood have been found and recruited, to date, vs. 5% of those not seen since childhood. Self-reported prevalences were 0.7% Type 1 Diabetes, 7.5% Type 2 Diabetes, 33% hypertension, and 12.8% CV event. 32% of CV events were judged to be true. I3C Outcomes is uniquely able to establish evidence-based guidelines for child health care and to clarify relations to adult CV disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: To detect novel loci with age-dependent effects on fasting (≥ 8 h) levels of total cholesterol, high-density lipoprotein, low-density lipoprotein, and triglycerides using 3600 African Americans, 1283 Asians, 3218 European Americans, and 2026 Mexican Americans from the Family Blood Pressure Program (FBPP)., Methods: Within each subgroup (defined by network, race, and sex), we employed stepwise linear regression (retention p ≤ 0.05) to adjust lipid levels for age, age-squared, age-cubed, body-mass-index, current smoking status, current drinking status, field center, estrogen therapy (females only), as well as antidiabetic, antihypertensive, and antilipidemic medication use. For each trait, we pooled the standardized male and female residuals within each network and race and fit a generalized variance components model that incorporated gene-age interactions. We conducted FBPP-wide and race-specific meta-analyses by combining the p-values of each linkage marker across subgroups using a modified Fisher's method., Results: We identified seven novel loci with age-dependent effects; four total cholesterol loci from the meta-analysis of Mexican Americans (on chromosomes 2q24.1, 4q21.21, 8q22.2, and 12p11.23) and three high-density lipoprotein loci from the meta-analysis of all FBPP subgroups (on chromosomes 1p12, 14q11.2, and 21q21.1). These loci lacked significant genome-wide linkage or association evidence in the literature and had logarithm of odds (LOD) score ≥ 3 in the meta-analysis with LOD ≥ 1 in at least two network and race subgroups (exclusively of non-European descent)., Conclusion: Incorporating gene-age interactions into the analysis of lipids using multi-ethnic cohorts can enhance gene discovery. These interaction loci can guide the selection of families for sequencing studies of lipid-associated variants., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objective: The association of familial as compared to genetic factors in the current obesogenic environment, compared with earlier, leaner time periods, is uncertain., Methods: Participants from the Framingham Heart Study were classified according to parental obesity status in the Original, Offspring, and Third Generation cohorts; mean BMI levels were estimated and we compared the association of parental history across generations. Finally, a genetic risk score comprised of 32 well-replicated single nucleotide polymorphisms for BMI was examined in association with BMI levels in 1948, 1971, and 2002., Results: BMI was 1.49 kg/m2 higher per each affected parent among the Offspring, and increased to 2.09 kg/m2 higher among the Third Generation participants (P-value for the cohort comparison=0.007). Parental history of obesity was associated with increased weight gain (P < 0.0001) and incident obesity (P = 0.009). Despite a stronger association of parental obesity with offspring BMI in more contemporary time periods, we observed no change in the effect size of a BMI genetic risk score from 1948 to 2002 (P = 0.11 for test of trend across the time periods)., Conclusions: The association of parental obesity has become stronger in more contemporary time period, whereas the association of a BMI genetic risk score has not changed., (Copyright © 2013 The Obesity Society.)

OBJECTIVE The metabolic syndrome (MetS) is defined as concomitant disorders of lipid and glucose metabolism, central obesity, and high blood pressure, with an increased risk of type 2 diabetes and cardiovascular disease. This study tests whether common genetic variants with pleiotropic effects account for some of the correlated architecture among five metabolic phenotypes that define MetS. RESEARCH DESIGN AND METHODS Seven studies of the STAMPEED consortium, comprising 22,161 participants of European ancestry, underwent genome-wide association analyses of metabolic traits using a panel of ∼2.5 million imputed single nucleotide polymorphisms (SNPs). Phenotypes were defined by the National Cholesterol Education Program (NCEP) criteria for MetS in pairwise combinations. Individuals exceeding the NCEP thresholds for both traits of a pair were considered affected. RESULTS Twenty-nine common variants were associated with MetS or a pair of traits. Variants in the genes LPL, CETP, APOA5 (and its cluster), GCKR (and its cluster), LIPC, TRIB1, LOC100128354/MTNR1B, ABCB11, and LOC100129150 were further tested for their association with individual qualitative and quantitative traits. None of the 16 top SNPs (one per gene) associated simultaneously with more than two individual traits. Of them 11 variants showed nominal associations with MetS per se. The effects of 16 top SNPs on the quantitative traits were relatively small, together explaining from ∼9% of the variance in triglycerides, 5.8% of high-density lipoprotein cholesterol, 3.6% of fasting glucose, and 1.4% of systolic blood pressure. CONCLUSIONS Qualitative and quantitative pleiotropic tests on pairs of traits indicate that a small portion of the covariation in these traits can be explained by the reported common genetic variants.

Background: A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension., Methods: We performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226 African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican-American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups., Results: Five quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score ≥3) in at least one meta-analysis and lod scores ≥1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses., Conclusions: The new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance.

Background: The etiology of cardiovascular disease (CVD) is multifactorial. Efforts to identify genes influencing CVD risk have met with limited success to date, likely because of the small effect sizes of common CVD risk alleles and the presence of gene by gene and gene by environment interactions., Methods: The HAPI Heart Study was initiated in 2002 to measure the cardiovascular response to 4 short-term interventions affecting cardiovascular risk factors and to identify the genetic and environmental determinants of these responses. The measurements included blood pressure responses to the cold pressor stress test and to a high salt diet, triglyceride excursion in response to a high-fat challenge, and response in platelet aggregation to aspirin therapy., Results: The interventions were carried out in 868 relatively healthy Amish adults from large families. The heritabilities of selected response traits for each intervention ranged from 8% to 38%, suggesting that some of the variation associated with response to each intervention can be attributed to the additive effects of genes., Conclusions: Identifying these response genes may identify new mechanisms influencing CVD and may lead to individualized preventive strategies and improved early detection of high-risk individuals.

Atherosclerotic cardiovascular disease (CVD) is a major health problem in the United States and around the world. Evidence accumulated over decades convincingly demonstrates that family history in a parent or a sibling is associated with atherosclerotic CVD, manifested as coronary heart disease, stroke, and/or peripheral arterial disease. Although there are several mendelian disorders that contribute to CVD, most common forms of CVD are believed to be multifactorial and to result from many genes, each with a relatively small effect working alone or in combination with modifier genes and/or environmental factors. The identification and the characterization of these genes and their modifiers would enhance prediction of CVD risk and improve prevention, treatment, and quality of care. This scientific statement describes the approaches researchers are using to advance understanding of the genetic basis of CVD and details the current state of knowledge regarding the genetics of myocardial infarction, atherosclerotic CVD, hypercholesterolemia, and hypertension. Current areas of interest and investigation--including gene-environment interaction, pharmacogenetics, and genetic counseling--are also discussed. The statement concludes with a list of specific recommendations intended to help incorporate usable knowledge into current clinical and public health practice, foster and guide future research, and prepare both researchers and practitioners for the changes likely to occur as molecular genetics moves from the laboratory to clinic.

The Family Blood Pressure Program (FBPP) has data on 387 microsatellite markers in 13,524 subjects from four major ethnic groups. We investigated genetic association with hypertension of the linkage markers. Family-based methods were used to test association of the 387 loci with resting blood pressures (BPs) [systolic blood pressure (SBP) and diastolic blood pressure (DBP)] and the hypertension status (HT). We applied a vote-counting approach to pool results across the three correlated traits, network samples, and ethnic groups to refine the selection of susceptibility loci. The association analyses captured signals missed by previous linkage scans. We found 71 loci associated with at least one of the three traits in at least one of the four ethnic groups at the significance level of 0.01. After validation across multiple samples and related traits, we identified by vote-counting 21 candidate loci for hypertension. Two loci, D3S2459 and D10S1412 confirmed findings in Network-specific linkage scans (GENOA and SAPPHIRe). Many of the candidate loci were reported by others in linkage to BPs, body weight, heart disease, and diabetes. We also observed frequent presence of quantitative trait loci (QTLs) involved in autoimmune and neurological disorders (e.g., NOD2). The vote-counting method of pooling results recognizes the potential that a gene may be involved in varying ways among different samples, which we believe is responsible for identifying genes in the less explored inflammatory pathways to hypertension.

Objective: This paper describes the preparation of genetic materials and the recruitment and initial characterization of a nested Family Study within the Jackson Heart Study (JHS) METHODS: Genomic DNA was prepared from all consenting JHS participants. In addition, family members of a subset of JHS participants were recruited to the JHS Family Study to allow heritability and linkage analyses and family-based association studies. Family Study participants completed the same questionnaires, measures, and procedures as all other JHS participants and provided blood samples for lymphocyte cryopreservation and transformation., Results: DNA samples were obtained from 4726 JHS participants, including 1499 members of 291 families. In the family cohort, estimated heritabilities of body mass index, selected lipid levels, and blood pressure are highly significant, supporting the validity of the sample., Discussion: The JHS data and genetic materials (DNA and cryopreserved cells) offer valuable opportunities to identify susceptibility alleles for common complex diseases by positional and candidate gene approaches.

Elevated plasma levels of C-reactive protein (CRP), an inflammation-sensitive marker, have emerged as an important predictor of future cardiovascular disease and metabolic abnormalities in apparently healthy men and women. Here, we performed a systematic survey of common nucleotide variation across the genomic region encompassing the CRP gene locus. Of the common single-nucleotide polymorphisms (SNPs) identified, several in the CRP promoter region are strongly associated with CRP levels in a large cohort study of cardiovascular risk in European American and African American young adults. We also demonstrate the functional importance of these SNPs in vitro.

Few studies of body composition have been done in New World primates. In the study reported here, four methods of assessing body composition (body weight, anthropometry, labeled-water dilution, and total body electroconductivity) were compared in 20 marmosets, aged 0.96 to 7.97 years. Males and females did not differ in any measure (P > 0.05). Body weight ranged from 272 to 466 g, and body fat estimates varied from 1.6 to 19.5%. Strong positive correlations were observed between total body water and total body electroconductivity (R2 = 0.77), body weight and fat-free mass (males R2 = 0.95; females R2 = 0.91), and body weight and fat mass (males R2 = 0.86; females R2 = 0.85; P < 0.01). Male and female slopes were equivalent (P > 0.05) for the regressions of fat and fat-free mass against body weight. Positive correlations also were observed between girth measures and fat-free mass (R2 = 0.48 to 0.78) and fat mass (R2 = 0.60 to 0.74; P < 0.01). A good second- order polynomial relationship was observed between age and fat-free mass for the combined sample (R2 = 0.64). Results indicated that: subjects were lean; there was no sexual dimorphism relative to measures; body weight provided a reliable estimate of fat and fat-free mass; and within-subject body weight changes reflected a similar relationship between body weight and fat-free mass as did that across subjects.

Significant relations were observed between select infant-care and weaning behaviors and growth in body weight in common marmoset monkeys (Callithrix jacchus). The patterns of these relations suggest that earlier occurrence of developmental milestones, such as cessation of transport (being off carriers) and weaning to solid food, were associated with slower growth during the subsequent period. In contrast, more frequent nursing bouts during the period in which weaning was initiated were associated with higher growth rates. In the case of being off carriers, these effects did not carry over to older ages, suggesting that any deficits in growth were temporary. In the case of earlier, more frequent consumption of solid food, there was some suggestion that there were longer-term effects, followed by catch-up growth. The knee-to-heel length of subjects was not related to the measured behaviors. There was no relation between early weaning to solid food and leanness at day 75, suggesting that, although this behavior was affecting overall weight, it did not affect relative gains of fat versus lean mass. There were, however, significant correlations between cessation of transport or frequency of nursing bouts during the weaning period and leanness, with earlier cessation of transport and less frequent nursing associated with leaner infants, after weaning. Our results differed from those of a previous study that found a relation between linear growth and abuse in this species, with abuse defined as physical injury by other members of the group. We found no differences in growth between abused and nonabused infants. However, abused infants had lower birth weight.

This report compares estimated gestational ages from published cubic spline curves to gestational ages estimated retrospectively from delivery dates in 28 pregnancies from ten common marmosets (Callithrix jacchus). Both CRL- and BPD-based estimates of gestational age were closely correlated with delivery-based gestational age estimates. Of the three ultrasound machines used, the one with 16 shades of gray and a sequential linear array overestimated gestational age during early pregnancy, based on CRL measures. Measures from the other two machines (64 or 264 shades of gray; linear sector and annular array or electronic phase array) were similar and resulted in a correlation of the two estimates of gestational age of 0.94 and a mean difference between the two estimates of 0.16 days with 80% of CRL-based gestational age estimates being within +/- 5 days of the delivery-based estimate. The reliability of BPD-based estimates of gestational age was strongly related to pregnancy outcome. BPD-based estimates underestimated gestational age in poor outcome pregnancies (i.e., those in which infants died within 7 days of birth) but not in good outcome pregnancies. The combined CRL- and BPD-based estimates on poor outcome pregnancies suggest that there was less growth in BPD in late gestation for those pregnancies that resulted in nonviable offspring. For good outcome pregnancies, the correlation between BPD-based and delivery-based estimates of gestational age was 0.871 and the mean difference between the two estimates was -0.06 days with 83.3% of BPD-based estimates falling within +/- 5 days of delivery-based estimates.

It is known that different genes are expressed during ontogeny; however, it is unclear how variation in that expression is associated with changes in growth patterns. The objective of this study is to assess how genetic variation in fetal morphology changes with ontogeny in baboons. Longitudinal measures of the head and femur (60 to 180 days gestation) were available for 892 pregnancies. We used a genetic model that allowed both the genetic and environmental variances (sigma 2G and sigma 2E) to change with age and estimated genetic and environmental correlations (rho G and rho E) between measurements at different ages. The results indicate a significant increase in the genetic variance for biparietal diameter and femur length but not for head circumference and fronto-occipital diameter. The rho G estimates for all measures decreased as the age between measures increased from 0 to 120 days, indicating that different groups of genes are expressed early in gestation and late in gestation. The rho E estimates dropped rapidly from 1 to 0 for all measures, indicating temporally localized environmental influences on fetal growth. Thus fetal morphometrics are significantly heritable and those genes that influence them show age-specific expression during ontogeny.

Sex hormone-binding globulin (SHBG) is a steroid-binding plasma protein with a high affinity for testosterone that has been inversely associated with cardiovascular disease risk in many populations. SHBG may also act as a receptor in some tissues. Although the function of SHBG is relatively well understood, comparatively little is known about genetic factors contributing to the normal variation of serum SHBG levels. We estimated the heritability (h2) of serum SHBG levels in 717 related Mexican-Americans participating in the San Antonio Family Heart Study (SAFHS). We found a significant heritability (h2 = 0.31, P < .0001) for serum SHBG levels; age, exogenous hormones, smoking status, diabetic status, and adiposity showed significant associations (P < .05) with mean levels of SHBG. Sex was associated with mean SHBG levels but not with genetic or environmental variance in SHBG levels; heritability estimates were the same for males and females. These results indicate a significant genetic influence on SHBG in Mexican-Americans. Thus, SHBG may prove to be an important indicator of genetic risk for cardiovascular disease in this population, as well as others.

The statistical properties of sib-pair and variance-components linkage methods were compared using the nuclear family data from Problem 2. Overall, the power to detect linkage was not high for either method. The variance-components method had better power for detection of linkage, particularly when covariates were included in the model. Type I error rates were similar to nominal error rates for both methods.

The relation between number of ovulations and body weight, age or maternal identity was examined in 69 ovarian cycles from 29 captive-born common marmoset monkeys (Callithrix jacchus). Specifically, we addressed the following questions: was there high repeatability of ovulation number? Most of the variation in ovulation number was within, rather than between subjects. Repeatability in number of ovulations was 0.081 (n = 20 females with 2-6 ovulatory cycles per female); was age related to number of ovulations? There was no relation between age and number of ovulations, either within or between subjects; and was weight related to number of ovulations? Weight was related to number of ovulations. When the relation between number of ovulations (1-2 versus 3-4) and weight was examined through a logistic regression, there was a significant relation. Also, of the 11 subjects which had a variable number of ovulations across cycles, 90.9% were heavier when ovulating 3-4 than when ovulating 2. These results are discussed as the basis for the proposal that callitrichid primates may have been selected for potential variation in reproductive output and that this variation may be related to energy availability.

Adult body mass and changes in mass during an individual's life are important indicators of general health and reproductive fitness. Therefore, characterization of the factors that influence normal variation in body mass has important implications for colony management and husbandry. The main objective of this study was to quantify the genetic contribution to adult body mass and its maintenance in baboons. Intra-individual mean and variance in body mass were calculated from multiple weight measures available for each of 1,614 animals at least 10 years of age. Heritabilities were estimated using maximum likelihood methods. Mean adult body mass had a significant heritability (50%) as did variance in adult body mass (12%). The sexes differed in several respects: on average females were smaller than males and had greater variability in adult body mass; mean and variance in body mass increased with age in females only; and number of offspring showed a significant positive relationship with body mass in females only. There were significant differences between subspecies in body mass as well as ability to maintain body mass. These results indicate that there is a significant genetic influence on body mass and its maintenance, and suggest that different factors influence changes in body mass with age as well as body mass maintenance in male and female baboons.

Dehydroepiandrosterone sulfate (DHEAS) is an adrenal steroid which has been inversely associated with development of atherosclerosis. We estimated heritability of serum DHEAS levels in 564 related Mexican Americans. We found a significant heritability for DHEAS (h2 = 0.39, p < 0.001). Measures of alcohol consumption, reproductive status, body composition, and HDL3 levels showed significant relationships with serum DHEAS levels. Sex and age were significantly associated with the mean, but not the genetic variance, of DHEAS levels. The results of this study demonstrate a significant genetic influence on steroid concentration and help to quantify the factors contributing to cardiovascular disease risk in Mexican Americans.

Previous studies have shown that the inverse relationship between HDL cholesterol (HDL-C) and triglyceride (TG) levels, risk factors for cardiovascular disease, is due largely to the effects of shared genes. HDL-C and TG are also known to be related to endogenous sex hormone levels, however the nature of the relationships is unclear. The objective of this study is to ascertain the extent to which these relationships are determined by shared genes. We conducted a multivariate quantitative genetic analysis of HDL-C, TG, dehydroepiandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) in 635 people from 27 pedigrees participating in the San Antonio Family Heart Study. Heritabilities (h2) and genetic and environmental correlations (rho G and rho E) were estimated simultaneously by maximum likelihood methods. All four traits showed significant (P < 0.05) heritabilities: h2HDL-C = 0.38, h2TG = 0.54, h2DHEAS = 0.43, h2SHBG = 0.26. Significant genetic correlations were detected between HDL and each of the other traits: rho G(HDL-TG) = -0.56, rho G(HDL-DHEAS) = 0.23 and rho G(HDL-SHBG) = -0.56. However, there were no significant genetic correlations between TG and either measure of sex hormones. Thus, at least three separate groups of genes influence HDL-C levels in Mexican Americans: one group that has pleiotropic effects on HDL and TG, one group influences both HDL-C and SHBG and a third influences both HDL-C and DHEAS.

Fifty common marmoset pregnancies were monitored using ultrasound. The objective was to ascertain if fetal mortality was related to litter size. Prior to analysis we determined abortion rate and litter size were not influenced by repeated ultrasound. Mortality was unrelated to litter size and occurred fairly late in gestation. All singletons born in this study began gestation as twins. It is hypothesized that marmosets may be able to adjust litter size late in pregnancy in response to proximate environmental factors.