Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations.
View Article and Find Full Text PDFLarge-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan.
View Article and Find Full Text PDFPartnered fathers often have lower testosterone than single non-parents, which is theorized to relate to elevated testosterone (T) facilitating competitive behaviors and lower T contributing to nurturing. Cultural- and individual-factors moderate the expression of such psychobiological profiles. Less is known about genetic variation's role in individual psychobiological responses to partnering and fathering, particularly as related to T.
View Article and Find Full Text PDFObjectives: Cross-species comparisons show that high extrinsic mortality favors the evolution of "faster" life histories. There is interest in applying this principle to human life history plasticity, based on the idea that psychosocial stressors that correlate with extrinsic mortality accelerate reproductive pace. Most prior studies have been conducted in settings in which psychosocial stressors co-occur with the maturation-accelerating influence of nutritional abundance.
View Article and Find Full Text PDFObjectives: We used detailed saliva sampling procedures to test for diurnal changes in men's salivary estradiol (E2) and testosterone (T) and assessed whether greater adiposity predicted higher E2 and T.
Methods: We drew on a subsample of young adults enrolled in a long-running birth cohort study in Metro Cebu, Philippines. Subjects provided saliva samples at four time points during the day (waking, waking +40 min, early evening, and bedtime), which were assayed for E2 and T.
Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 × 10(-8), including 62 loci not previously associated with lipid levels in humans.
View Article and Find Full Text PDFTriglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 × 10(-8) for each) to examine the role of triglycerides in risk for CAD.
View Article and Find Full Text PDFBlood levels of lipoprotein cholesterol and triglycerides (TGs) are highly heritable and are major risk factors for cardiovascular disease (CVD). Approximately 100 lipid-associated loci have been identified in populations of European ancestry. We performed a genome-wide association study of lipid traits in 1,782 Filipino women from the Cebu Longitudinal Health and Nutrition Survey, and tested for evidence of interactions with waist circumference.
View Article and Find Full Text PDFTestosterone (T) is thought to help facilitate trade-offs between mating and parenting in humans. Across diverse cultural settings married men and fathers have lower T than other men and couples' sexual activity often declines during the first years of marriage and after having children. It is unknown whether these behavioral and hormonal changes are related.
View Article and Find Full Text PDFGenome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants.
View Article and Find Full Text PDFAlthough humans are considered unusual among mammals for the intensity of care that fathers often provide offspring, little is known about the hormonal architecture regulating human paternal investment. Prolactin has important reproductive functions in both female and male mammals and other taxa, making it a candidate regulator of human paternal behavior. Notably, prolactin is higher during periods of offspring care in some species, but it is unknown if this pattern occurs in human fathers.
View Article and Find Full Text PDFCirculating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.
View Article and Find Full Text PDFObjectives: Lower birth weight (BW) reoccurs across generations, but the intermediate mechanisms remain poorly understood. One potential pathway involves cortisol, which may be elevated in women born small and in turn could lead to fetal growth restriction in offspring. To test this possibility, we evaluated whether BW predicts hypothalamic-pituitary-adrenal (HPA) function in the nonpregnant state in a cohort of young Filipino women, and whether differences in HPA function predict offspring BW.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2011
In species in which males care for young, testosterone (T) is often high during mating periods but then declines to allow for caregiving of resulting offspring. This model may apply to human males, but past human studies of T and fatherhood have been cross-sectional, making it unclear whether fatherhood suppresses T or if men with lower T are more likely to become fathers. Here, we use a large representative study in the Philippines (n = 624) to show that among single nonfathers at baseline (2005) (21.
View Article and Find Full Text PDFCoconut oil is a common edible oil in many countries, and there is mixed evidence for its effects on lipid profiles and cardiovascular disease risk. Here we examine the association between coconut oil consumption and lipid profiles in a cohort of 1,839 Filipino women (age 35-69 years) participating in the Cebu Longitudinal Health and Nutrition Survey, a community based study in Metropolitan Cebu. Coconut oil intake was estimated using the mean of two 24-hour dietary recalls (9.
View Article and Find Full Text PDFObjectives: Inflammation has been associated with a wide range of chronic degenerative diseases, but the developmental factors contributing to the regulation of inflammation are poorly understood. This study investigates the within-individual association between antibody response to vaccination in adolescence and C-reactive protein (CRP) concentration in young adulthood.
Methods: In 1998-99, at age 14-15 years, a subset of participants (N = 96) in the Cebu Longitudinal Health and Nutrition Survey were administered a typhoid vaccine, and baseline and follow-up blood samples were drawn to assess the strength of the antibody response to vaccination.
Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P < 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time.
View Article and Find Full Text PDFCardiovascular disease (CVD) is a leading cause of death in the Philippines, although few studies here have examined the lipid profiles underlying disease risk. The isolated low high density lipoprotein cholesterol (HDL-c) phenotype has been implicated as a CVD risk factor, the prevalence of which exhibits significant variation across populations. To assess population variation in individual lipid components and their associations with diet and anthropometric characteristics, we compare lipid profiles in a population of adult Filipino women (n=1877) to US women participating in the National Health and Nutrition Examination Survey (NHANES, n=477).
View Article and Find Full Text PDFIn species with a high level of paternal care, including humans, testosterone (T) is believed to help mediate the trade-off between parenting and mating effort. This hypothesis is supported by the observation of lower T in pairbonded men or fathers compared to single, non-fathers; however, prior work has highlighted population variation in the association between T and pairbonding or fatherhood status. Here we evaluate this hypothesis in a large (n=890), representative birth cohort of young men (age range 20.
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