Dataset Information

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

ABSTRACT: Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants between Europeans and Africans have several unique determinants. The common variant rs12740374 associated with Lp(a) cholesterol is an eQTL for SORT1 and independent of LDL cholesterol. Observed associations of aggregates of rare non-coding variants are largely explained by LPA structural variation, namely the LPA kringle IV 2 (KIV2)-CN. Finally, we find that LPA risk genotypes confer greater relative risk for incident atherosclerotic cardiovascular diseases compared to directly measured Lp(a), and are significantly associated with measures of subclinical atherosclerosis in African Americans.

SUBMITTER: Zekavat SM

PROVIDER: S-EPMC6031652 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Zekavat Seyedeh M SM Ruotsalainen Sanni S Handsaker Robert E RE Alver Maris M Bloom Jonathan J Poterba Timothy T Seed Cotton C Ernst Jason J Chaffin Mark M Engreitz Jesse J Peloso Gina M GM Manichaikul Ani A Yang Chaojie C Ryan Kathleen A KA Fu Mao M Johnson W Craig WC Tsai Michael M Budoff Matthew M Vasan Ramachandran S RS Cupples L Adrienne LA Rotter Jerome I JI Rich Stephen S SS Post Wendy W Mitchell Braxton D BD Correa Adolfo A Metspalu Andres A Wilson James G JG Salomaa Veikko V Kellis Manolis M Daly Mark J MJ Neale Benjamin M BM McCarroll Steven S Surakka Ida I Esko Tonu T Ganna Andrea A Ripatti Samuli S Kathiresan Sekar S Natarajan Pradeep P

Nature communications 20180704 1

Lipoprotein(a), Lp(a), is a modified low-density lipoprotein particle that contains apolipoprotein(a), encoded by LPA, and is a highly heritable, causal risk factor for cardiovascular diseases that varies in concentrations across ancestries. Here, we use deep-coverage whole genome sequencing in 8392 individuals of European and African ancestry to discover and interpret both single-nucleotide variants and copy number (CN) variation associated with Lp(a). We observe that genetic determinants betwe ...[more]

PMID: 29973585

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Project description:BackgroundIntra-continentally, vaginal microbiome signatures are reported to be significantly different between Black and Caucasian women, with women of African ancestry having the less well defined heterogenous bacterial community state type (CST) deficient of Lactobacillus species (CST IV). The objective of this study was to characterize the vaginal microbiomes across a more diverse intercontinental group of women (N = 151) of different ethnicities (African American, African Kenyan, Afro-Caribbean, Asian Indonesian and Caucasian German) using 16S rRNA gene sequence analysis to determine their structures and offer a comprehensive description of the non-Lactobacillus dominant CSTs and subtypes.ResultsIn this study, the bacterial composition of the vaginal microbiomes differed significantly among the ethnic groups. Lactobacillus spp. (L. crispatus and L. iners) dominated the vaginal microbiomes in African American women (91.8%) compared to European (German, 42.4%), Asian (Indonesian, 45.0%), African (Kenyan, 34.4%) and Afro-Caribbean (26.1%) women. Expanding on CST classification, three subtypes of CST IV (CST IV-A, IV-B and IV-C) (N = 56, 37.1%) and four additional CSTs were described: CST VI Gardnerella vaginalis-dominant (N = 6, 21.8%); CST VII (Prevotella-dominant, N = 1, 0.66%); CST VIII (N = 9, 5.96%), resembling aerobic vaginitis, was differentiated by a high proportion of taxa such as Enterococcus, Streptococcus and Staphylococcus (relative abundance [RA] > 50%) and CST IX (N = 7, 4.64%) dominated by genera other than Lactobacillus, Gardnerella or Prevotella (e.g., Bifidobacterium breve and Anaerococcus vaginalis). Within the vaginal microbiomes, 32 "taxa with high pathogenic potential" (THPP) were identified. Collectively, THPP (mean RA ~5.24%) negatively correlated (rs = -0.68, p < 2.2e-16) with Lactobacillus species but not significantly with Gardnerella/Prevotella spp. combined (r = -0.13, p = 0.1). However, at the individual level, Mycoplasma hominis exhibited moderate positive correlations with Gardnerella (r = 0.46, p = 2.6e-09) and Prevotella spp. (r = 0.47, p = 1.4e-09).ConclusionsThese findings while supporting the idea that vaginal microbiomes vary with ethnicity, also suggest that CSTs are more wide-ranging and not exclusive to any particular ethnic group. This study offers additional insight into the structure of the vaginal microbiome and contributes to the description and subcategorization of non-Lactobacillus-dominated CSTs.

Dataset Information

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Publications

Deep coverage whole genome sequences and plasma lipoprotein(a) in individuals of European and African ancestries.

Similar Datasets

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