Vitamin D status affects proteomic profile of HDL-associated proteins and inflammatory mediators in dyslipidemia.

Vitamin D deficiency and dyslipidemia have substantial implications for human health globally. Vitamin D is essential for bone metabolism and immune modulation, and its insufficiency is linked to various chronic inflammatory conditions. Dyslipidemia, characterized by low levels of high-density lipoprotein (HDL) and elevated levels of low-density lipoprotein (LDL) and triglycerides, is also prevalent. Previous research has shown a connection between vitamin D deficiency and low HDL, but the precise mechanism by which vitamin D influences HDL production and its anti-inflammatory properties remains unclear. This study aimed to investigate the proteomic profiles of individuals with and without vitamin D deficiency and dyslipidemia, specifically focusing on the effects of vitamin D on HDL production, its anti-inflammatory potential, and the molecular pathways associated with vitamin D deficiency and dyslipidemia, particularly inflammation and cancer pathways. By analyzing the proteomic profiles of 274 participants from the Qatar Biobank database, we identified 1301 proteins. Our findings indicated a decrease in HDL-associated apolipoproteins (ApoM and ApoD) in individuals with both dyslipidemia and vitamin D deficiency. Conversely, participants with these conditions exhibited increased expression of acute-phase proteins (SAA1 and SOD1), which are associated with inflammation. Pathway enrichment analysis revealed heightened inflammatory activity in individuals with vitamin D deficiency and dyslipidemia, with notable enrichments in pathways such as MAPK, JAK-STAT, Ras signaling, cytokine-cytokine receptor interaction, AGE-RAGE, ErbB signaling, and cancer pathways. Overall, cases of vitamin D deficiency showed enrichment in inflammation pathways, while individuals with both vitamin D deficiency and dyslipidemia demonstrated enhanced activation of cancer and inflammation pathways.

Thousands of Qatari genomes inform human migration history and improve imputation of Arab haplotypes.

Arab populations are largely understudied, notably their genetic structure and history. Here we present an in-depth analysis of 6,218 whole genomes from Qatar, revealing extensive diversity as well as genetic ancestries representing the main founding Arab genealogical lineages of Qahtanite (Peninsular Arabs) and Adnanite (General Arabs and West Eurasian Arabs). We find that Peninsular Arabs are the closest relatives of ancient hunter-gatherers and Neolithic farmers from the Levant, and that founder Arab populations experienced multiple splitting events 12-20 kya, consistent with the aridification of Arabia and farming in the Levant, giving rise to settler and nomadic communities. In terms of recent genetic flow, we show that these ancestries contributed significantly to European, South Asian as well as South American populations, likely as a result of Islamic expansion over the past 1400 years. Notably, we characterize a large cohort of men with the ChrY J1a2b haplogroup (n = 1,491), identifying 29 unique sub-haplogroups. Finally, we leverage genotype novelty to build a reference panel of 12,432 haplotypes, demonstrating improved genotype imputation for both rare and common alleles in Arabs and the wider Middle East.