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Objective: This analysis assessed the putative causal association between genetically predicted percent body fat and areal bone mineral density (aBMD) and, more specifically, the association between genetically predicted metabolically "favorable adiposity" (MFA) and aBMD at clinically relevant bone sites. Methods: Mendelian randomization was used to assess the relationship of MFA and percent body fat with whole‐body, lumbar spine, femoral neck, and forearm aBMD. Sex‐stratified and age‐stratified exploratory analyses were conducted. Results: In all MR analyses, genetically predicted MFA was inversely associated with aBMD for the whole body (β = −0.053, p = 0.0002), lumbar spine (β = −0.075; p = 0.0001), femoral neck (β = −0.045; p = 0.008), and forearm (β = −0.115; p = 0.001). This negative relationship was strongest in older individuals and did not differ by sex. The relationship between genetically predicted percent body fat and aBMD was nonsignificant across all Mendelian randomization analyses. Several loci that were associated at a genome‐wide significance level (p < 5 × 10−8) in opposite directions with body fat and aBMD measures were also identified. Conclusions: This study did not support the hypothesis that MFA protects against low aBMD. Instead, it showed that MFA may result in lower aBMD. Further research is needed to understand how MFA affects aBMD and other components of bone health such as bone turnover, bone architecture, and osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Objectives To determine whether the relationship between anthropometric measurements of obesity and mortality varies according to age, race, and ethnicity in older women. Design Prospective cohort study of multiethnic postmenopausal women. Setting Women's Health Initiative ( WHI) observational study and clinical trials in 40 clinics. Participants Postmenopausal women aged 50-79 participating in WHI (N = 161,808). Measurements Baseline height, weight, and waist circumference ( WC) were measured, and body mass index ( BMI) was calculated based on height and weight. Demographic, health, and lifestyle data from a baseline questionnaire were used as covariates. The outcome was adjudicated death (n = 18,320) during a mean follow-up of 11.4 ± 3.2 years. Results Hazard ratios ( HRs) and 95% confidence intervals (95% CIs) indicated that ethnicity and age modified ( P < .01) the relationship between obesity and mortality. Underweight was associated with higher mortality, but overweight or slight obesity was not a risk factor for mortality in most ethnic groups except for Hispanic women in the obesity I category ( HR = 1.42, 95% CI = 1.04-1.95). BMI was not or was only weakly associated with mortality in individuals aged 70-79 ( HR = 0.90, 95% CI = 0.85-0.95 for overweight; HR = 0.98, 95 CI = 0.92-1.06 for obese I; HR = 1.11, 95% CI = 1.00-1.23 for obese II; HR = 1.08, 95% CI = 0.92-1.26 for obese III). In contrast, higher central obesity measured using WC was consistently associated with higher mortality in all groups. Conclusion Underweight is a significant risk factor for mortality in older women, and healthy BMI ranges may need to be specific for age, race, and ethnicity. The findings support a consistent relationship between central obesity and mortality. [ABSTRACT FROM AUTHOR]

Background Genome-wide association studies ( GWAS) have identified single nucleotide polymorphisms ( SNPs) associated with type 2 diabetes ( T2D), mainly among individuals of European ancestry. In the present study, we examined the frequency of these SNPs and their association with T2D-related traits in an Alaska Native study population with a historically low prevalence of T2D. We also investigated whether dietary characteristics that may protect against T2D, such as n-3 polyunsaturated fatty acid ( PUFA) intake, modify these associations. Methods In 1144 Yup'ik people, we examined 17 SNPs repeatedly identified in GWAS for individual and cumulative associations with T2D-related traits. Cumulative associations were evaluated using a genetic risk score ( GRS) calculated by summing risk alleles. Associations were tested for interactions with sex, body mass index ( BMI), and n-3 PUFA intake. Results The rs7754840 SNP in CDKAL1 is significantly associated with HbA1c ( P = 0.00091). The rs5015480 SNP near HHEX is significantly associated (in opposite direction to that in Europeans) with a combined fasting glucose ( FG) and HbA1c measure ( P = 0.00046) and with homeostatic model assessment of β-cell function ( HOMA- B; P = 0.0014). The GRS is significantly associated with FG and combined FG and HbA1c only when the HHEX SNP is dropped from the GRS. Associations are not modified by BMI or n-3 PUFA intake. Conclusion Our results highlight the potential importance of CDKAL1 and HHEX in glucose homeostasis in this Alaska Native population with a low prevalence of T2D, and suggest that these loci should be examined in greater detail in this population. [ABSTRACT FROM AUTHOR]

Objectives To identify genomic regions associated with fasting plasma lipid profiles, insulin, glucose, and glycosylated hemoglobin in a Yup'ik study population, and to evaluate whether the observed associations between genetic factors and metabolic traits were modified by dietary intake of marine derived omega-3 polyunsaturated acids (n-3 PUFA). Methods A genome-wide linkage scan was conducted among 982 participants of the Center for Alaska Native Health Research study. n-3 PUFA intake was estimated using the nitrogen stable isotope ratio (δ15N) of erythrocytes. All genotyped SNPs located within genomic regions with LOD scores > 2 were subsequently tested for individual SNP associations with metabolic traits using linear models that account for familial correlation as well as age, sex, community group, and n-3 PUFA intake. Separate linear models were fit to evaluate interactions between the genotype of interest and n-3 PUFA intake. Results We identified several chromosomal regions linked to serum apolipoprotein A2, high density lipoprotein-, low density lipoprotein-, and total cholesterol, insulin, and glycosylated hemoglobin. Genetic variants found to be associated with total cholesterol mapped to a region containing previously validated lipid loci on chromosome 19, and additional novel peaks of biological interest were identified at 11q12.2-11q13.2. We did not observe any significant interactions between n-3 PUFA intake, genotypes, and metabolic traits. Conclusions We have completed a whole genome linkage scan for metabolic traits in Native Alaskans, confirming previously identified loci, and offering preliminary evidence of novel loci implicated in chronic disease pathogenesis in this population. Am. J. Hum. Biol., 25:673-680, 2013. © 2013 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

The relationship between ethnicity and biology is of interest to anthropologists, biomedical scientists, and historians in understanding how human groups are constructed. Ethnic self-identification in recently admixed groups such as Hispanics, African Americans, and Native Americans (NA) is likely to be complex due to the heterogeneity in individual admixture proportions and social environments within these groups. This study examines the relationships between self-identified ethnicity, self-estimated admixture proportions, skin pigmentation, and genetic marker estimated admixture proportions. These measures were assessed using questionnaires, skin color measurements, and genotyping of a panel of 76 ancestry informative markers, among 170 Hispanics and NAs from New Mexico, a state known for its complex history of interactions between people of NA and European (EU) ancestry. Results reveal that NAs underestimate their degree of EU admixture, and that Hispanics underestimate their degree of NA admixture. Within Hispanics, genetic-marker estimated admixture is better predicted by forehead skin pigmentation than by self-estimated admixture. We also find that Hispanic individuals self-identified as "half-White, half Hispanic" and "Spanish" have lower levels of NA admixture than those self-identified as "Mexican" and "Mexican American." Such results highlight the interplay between culture and biology in how individuals identify and view themselves, and have implications for how ethnicity and disease risk are assessed in a medical setting.