Heritability, the proportion of phenotypic variance explained by genetic factors, can be estimated from pedigree data 1 , but such estimates are uninformative with respect to the underlying genetic architecture. Analyses of data from genome-wide association studies (GWAS) on unrelated individuals have shown that for human traits and disease, approximately one-third to two-thirds of heritability is captured by common SNPs 2-5 . It is not known whether the remaining heritability is due to the imperfect tagging of causal variants by common SNPs, in particular if the causal variants are rare, or other reasons such as overestimation of heritability from pedigree data. Here we show that pedigree heritability for height and body mass index (BMI) appears to be fully recovered from whole-genome sequence (WGS) data on 21,620 unrelated individuals of European ancestry. We assigned 47.1 million genetic variants to groups based upon their minor allele frequencies (MAF) and linkage disequilibrium (LD) with variants nearby, and estimated and partitioned variation accordingly. The estimated heritability was 0.79 (SE 0.09) for height and 0.40 (SE 0.09) for BMI, consistent with pedigree estimates. Low-MAF variants in low LD with neighbouring variants were enriched for heritability, to a greater extent for protein altering variants, consistent with negative selection thereon. Cumulatively variants in the MAF range of 0.0001 to 0.1 explained 0.54 (SE 0.05) and 0.51 (SE 0.11) of heritability for height and BMI, respectively. Our results imply that the still missing heritability of complex traits and disease is accounted for by rare variants, in particular those in regions of low LD.

Background The prevalence of hypertension and diabetes are expected to increase in sub-Saharan Africa over the next decade. Some studies have documented that lifestyle factors and lack of awareness are directly influencing the control of these diseases. Yet, few studies have attempted to understand the barriers to control of these conditions in rural settings. The main objective of this study was to understand the challenges to hypertension and diabetes care in rural Uganda. Methods We conducted semi-structured interviews with 24 patients with hypertension and/or diabetes, 11 health care professionals (HCPs), and 12 community health workers (known as village health team members [VHTs]) in Nakaseke District, Uganda. Data were coded using NVivo software and analyzed using a thematic approach. Results The results replicated several findings from other settings, and identified some previously undocumented challenges including patients’ knowledge gaps regarding the preventable aspects of HTN and DM, patients’ mistrust in the Ugandan health care system rather than in individual HCPs, and skepticism from both HCPs and patients regarding a potential role for VHTs in HTN and DM management. Conclusions In order to improve hypertension and diabetes management in this setting, we recommend taking actions to help patients to understand NCDs as preventable, for HCPs and patients to advocate together for health system reform regarding medication accessibility, and for promoting education, screening, and monitoring activities to be conducted on a community level in collaboration with village health team members.

Fine-mapping to plausible causal variation may be more effective in multi-ancestry cohorts, particularly in the MHC, which has population-specific structure. To enable such studies, we constructed a large ( n = 21,546) HLA reference panel spanning five global populations based on whole-genome sequences. Despite population specific long-range haplotypes, we demonstrated accurate imputation at G-group resolution (94.2%, 93.7%, 97.8% and 93.7% in Admixed African (AA), East Asian (EAS), European (EUR) and Latino (LAT) populations). Applying HLA imputation to genome-wide association study (GWAS) data for HIV-1 viral load in three populations (EUR, AA and LAT), we obviated effects of previously reported associations from population-specific HIV studies and discovered a novel association at position 156 in HLA-B. We pinpointed the MHC association to three amino acid positions (97, 67 and 156) marking three consecutive pockets (C, B and D) within the HLA-B peptide binding groove, explaining 12.9% of trait variance.

Background: Breastfeeding is a critical, evidence-based intervention that addresses malnutrition, improves early childhood development outcomes, and influences long-term maternal and infant health by reducing the noncommunicable disease risk. Scaling up breastfeeding is an indisputably strong action countries can take to prevent suboptimal maternal and infant health outcomes. The Becoming Breastfeeding Friendly (BBF) initiative assists countries with scaling up breastfeeding policy and programs. BBF has been successfully implemented within Latin America, Africa, Europe and SouthEast Asian regions. This study assessed its application in Samoa. Methods: In 2018, BBF was implemented in Samoa by a 20 member committee of breastfeeding experts who participated in collecting and utilizing national level data to score the degree of friendliness of Samoa's breastfeeding environment, identify gaps, and propose policy recommendations to address those gaps. This eightmonth process resulted in a public event where priority recommendations were widely disseminated to decision makers and actions agreed upon. Results: The total BBF Index score for Samoa was 1.6 out of 3.0, indicating a moderate breastfeeding friendly environment for scaling up policies and programs that protect, promote, and support breastfeeding. Gear total scores indicated that seven of the eight gears were moderately strong within Samoa, while the eighth gear, funding and resources, was weakest in strength. Six prioritized recommendations emerged: 1) development and implementation of a National Breastfeeding Policy and Strategic Action Plan; 2) strengthening monitoring and evaluation of all breastfeeding activities; 3) ratifying the International Labour Organization's Maternity Protection Convention 2000 (No 183); 4) identifying high-level advocates to champion and serve as role models for breastfeeding; 5) creation of a national budget line for breastfeeding activities; and 6) hiring of a national breastfeeding coordinator and trainer. Decision makers demonstrated commitment by signing the breastfeeding policy for hospitals ahead of the BBF dissemination meeting and electing to move forward with establishing lactation rooms within government ministries. Conclusion: Implementation of BBF in Samoa yielded important policy recommendations that will address current gaps in national level breastfeeding support. The BBF consultation process can be successfully applied to other countries within the Western Pacific region in order to strengthen their breastfeeding programs.

Objectives Pacific Islanders are disproportionately burdened by poorer perinatal health outcomes with higher rates of pre-term births, low birth weight babies, infant mortality, and inadequate or no prenatal care. The aim of this study is to examine Marshallese mothers' beliefs, perceptions, and experiences of prenatal care and to identify potential barriers. Methods Three focus groups were conducted with Marshallese mothers, who were 18 years or older, and living in Arkansas. Focus groups focused on mothers' beliefs, perceptions, and experiences of prenatal care. A thematic qualitative analysis was conducted to identify salient themes within the data. Results The results demonstrated that negotiating health insurance, transportation, and language barriers were all major structural barriers that constrain prenatal care. The social-cultural barriers that emerged included a lack of understanding of the importance of seeking early and consistent prenatal care, as well as how to navigate the healthcare process. The more complicated challenges that emerged were the feelings of shame and embarrassment due to the perception of their age or being unmarried during pregnancy not being acceptable in American culture. Furthermore, the participants described perceived discrimination from prenatal care providers. Lastly, the participants described fear as a barrier to seeking out prenatal care. Conclusions for Practice This study identified both structural and socio-cultural barriers that can be incorporated into suggestions for policy makers to aid in alleviating maternal health disparities among Pacific Islander women. Further research is needed to address the Marshallese mothers' perceived discrimination from maternal health care providers.