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1.
Curr Biol ; 29(22): 3953-3959.e4, 2019 Nov 18.
Artículo en Inglés | MEDLINE | ID: mdl-31679935

RESUMEN

North Africa is located at the crossroads of the Mediterranean Sea, the Middle East, and the Sahara Desert. Extensive migrations and gene flow in the region have shaped many different cultures and ancestral genetic components through time [1-6]. DNA data from ancient Moroccan sites [7, 8] has recently shed some light to the population continuity-versus-replacement debate, i.e., the question of whether current North African populations descend from Palaeolithic groups or, on the contrary, subsequent migrations swept away all pre-existing genetic signal in the region. In the present study, we analyze 21 complete North African genomes and compare them with extant and ancient genome data in order to address the demographic continuity-versus-replacement debate, to assess whether these demographic events were homogeneous (including Berber and Arabic-speaking groups), and to explore the effect of Neolithization and posterior migration waves. The North African genetic pool is defined as a melting pot of genetic components, including an endemic North African Epipalaeolithic component at low frequency that forms a declining gradient from Western to Eastern North Africa. This scenario is consistent with Neolithization having shaped most of the current genetic variation in the region when compared to posterior back-to-North-Africa migration waves such as the Arabization. A common and distinct genetic history of the region is shown, with internal different proportions of genetic components owing to differential admixture with surrounding groups as well as to genetic drift due to isolation and endogamy in certain populations.

2.
PLoS One ; 14(8): e0221672, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31437235

RESUMEN

[This corrects the article DOI: 10.1371/journal.pone.0218443.].

3.
J Diabetes Metab Disord ; 18(1): 163-172, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31275887

RESUMEN

Background: A two-way relationship between diabetes and periodontitis is now clinically established. Both conditions share common mechanisms of pathogenesis that are related to altered immune-inflammatory responses at local and/or systemic levels. The aim of this study is to investigate whether periodontitis is associated with the development and progression of diabetes and to evaluate the health impact of coexistence of both diseases. Material and methods: Male Sprague Dawley rats (10 weeks old) were randomized into seven groups (n = 12): Group 1) Control; Groups 2 and 6) Periodontitis induced at two or six weeks; Groups 3 and 5) Diabetes induced at two or six weeks; Groups 4 and 7) Periodontitis followed by diabetes, and diabetes followed by periodontitis at two or six weeks. For diabetes induction, animals received a one-time intravenous injection of streptozotocin (50 mg/kg). Periodontitis was induced by Lipoppolysaccharide injection (20 µg/rat) through the palatal gingival and by placing a ligature of 0/0 braided silk around the cervix of the upper right second molar. Body weight, glycaemia as well as urine were collected weekly. Rats were sacrificed at the end of week 10, gingival tissue was removed, fixed in formaldehyde and processed for histopathological study. Results: Body weight was significantly decreased (25%) following diabetes induction (p < 0.01). 40% weight loss was observed when diabetes was induced first compared to 30% when periodontitis was first induced in the animals (p < 0.01). Rats treated with streptozotocin showed a three-fold increase in diabetes compared to the control group (p < 0.01). In rats where periodontitis was induced after diabetes, glucose levels increased significantly (450 mg/dL) compared to glucose levels (410 mg/dL) where periodontitis was induced first (p < 0.01). Histopathological studies showed greater alveolar bone loss when both diabetes and periodontitis were present. Conclusion: When periodontitis occurs after diabetes it aggravates the symptoms of the two pathologies. When diabetes is induced after periodontitis, no symptoms aggravation is observed for diabetes, although periodontitis gets worse.

4.
PLoS One ; 14(6): e0218443, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31211820

RESUMEN

Low serum levels of high-density lipoprotein cholesterol (HDL-C) have been shown to be a risk factor for coronary artery disease independent of low-density lipoprotein cholesterol (LDL-C) in different populations. In this study, we investigated genetic variants through genome-wide association studies to determine their association with HDL-C levels in a sample of 2,700 patients. We identified several SNPs associated with HDL-C levels in the Lebanese population using unadjusted and adjusted by biological factors models. We replicated the association of rs3764261 within CETP with HDL-C levels in the study population, and found other previously unidentified SNPs to be significant at the suggestive level, in both previously identified and unidentified genes. This paper reports the first genome-wide analysis of HDL-C in the Lebanese, Middle Eastern, population and supports the importance of genome-wide association studies across different and minor ethnicities to understand better the etiology of complex human diseases.

5.
Genome Biol ; 20(1): 77, 2019 04 26.
Artículo en Inglés | MEDLINE | ID: mdl-31023378

RESUMEN

BACKGROUND: Population demography and gene flow among African groups, as well as the putative archaic introgression of ancient hominins, have been poorly explored at the genome level. RESULTS: Here, we examine 15 African populations covering all major continental linguistic groups, ecosystems, and lifestyles within Africa through analysis of whole-genome sequence data of 21 individuals sequenced at deep coverage. We observe a remarkable correlation among genetic diversity and geographic distance, with the hunter-gatherer groups being more genetically differentiated and having larger effective population sizes throughout most modern-human history. Admixture signals are found between neighbor populations from both hunter-gatherer and agriculturalists groups, whereas North African individuals are closely related to Eurasian populations. Regarding archaic gene flow, we test six complex demographic models that consider recent admixture as well as archaic introgression. We identify the fingerprint of an archaic introgression event in the sub-Saharan populations included in the models (~ 4.0% in Khoisan, ~ 4.3% in Mbuti Pygmies, and ~ 5.8% in Mandenka) from an early divergent and currently extinct ghost modern human lineage. CONCLUSION: The present study represents an in-depth genomic analysis of a Pan African set of individuals, which emphasizes their complex relationships and demographic history at population level.


Asunto(s)
Grupo de Ascendencia Continental Africana/genética , Flujo Génico , Migración Humana , África , Variación Genética , Humanos , Filogeografía , Densidad de Población , Secuenciación Completa del Genoma
6.
J Clin Transl Endocrinol ; 16: 100185, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30899673

RESUMEN

Aims: The Middle East has the fastest rising rate of Type 2 Diabetes Mellitus (T2DM) worldwide, with Lebanon having 15.8% of its population affected. This study aims at studying Polycystic Ovarian Syndrome (PCOS), Gestational Diabetes Mellitus (GDM), and macrosomia as risk factors of T2DM in Lebanon. Such epidemiological and statistical study has never been conducted before in the Middle East region and would be useful for clinical diagnosis. Methods: Our cohort is comprised of 1453 Lebanese individuals, with 897 controls and 556 patients. We tested the correlation between T2DM and the covariates GDM, PCOS, and macrosomia independently. We conducted multinomial logistic regression and cross tabulations with T2DM as an outcome. Results: The results showed a significant association of the independent factors GDM and macrosomia with T2DM. The risk of having T2DM was increased by 4.192 times with the GDM, and by 2.315 times with macrosomia respectively. Conclusion: In conclusion, GDM and macrosomia, but not PCOS, are significant risk factors for T2DM in our Lebanese cohort. Our results, reported for the first time in the Middle East, present insights into risk factors management and disease prevention.

7.
Lipids Health Dis ; 18(1): 38, 2019 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-30711004

RESUMEN

BACKGROUND: Lipoproteins are major players in the development and progression of atherosclerotic plaques leading to coronary stenosis and myocardial infarction. Epidemiological, genetic and experimental observations have implicated the association of sphingolipids and intermediates of sphingolipid synthesis in atherosclerosis. We aimed to investigate relationships between quantitative changes in serum sphingolipids, the regulation of the metabolism of lipoproteins (LDL, HDL), and endophenotypes of coronary artery disease (CAD). METHODS: We carried out untargeted liquid chromatography - mass spectrometry (UPLC-MS) lipidomics of serum samples of subjects belonging to a cross-sectional study and recruited on the basis of absence or presence of angiographically-defined CAD, and extensively characterized for clinical and biochemical phenotypes. RESULTS: Among the 2998 spectral features detected in the serum samples, 1328 metabolic features were significantly correlated with at least one of the clinical or biochemical phenotypes measured in the cohort. We found evidence of significant associations between 34 metabolite signals, corresponding to a set of sphingomyelins, and serum HDL cholesterol. Many of these metabolite associations were also observed with serum LDL and total cholesterol levels but not as much with serum triglycerides. CONCLUSION: Among patients with CAD, sphingolipids in the form of sphingomyelins are directly correlated with serum levels of lipoproteins and total cholesterol. Results from this study support the fundamental role of sphingolipids in modulating lipid serum levels, highlighting the importance to identify novel targets in the sphingolipid metabolic pathway for anti-atherogenic therapies.


Asunto(s)
Colesterol/sangre , Esfingomielinas/sangre , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/sangre , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Espectrometría de Masas , Metabolómica/instrumentación , Metabolómica/métodos , Persona de Mediana Edad , Adulto Joven
8.
Eur J Hum Genet ; 27(6): 941-951, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-30765884

RESUMEN

In this study, we seek to understand and to correlate the genetic patterns observed in the population of the island of Ibiza in the Western Mediterranean basin with past events. Genome-wide genotypes of 189 samples representing 13 of 17 regions in Spain have been analyzed, in addition to 105 samples from the Levant, 157 samples from North Africa, and one ancient sample from the Phoenician Cas Molí site in Ibiza. Before the Catalans conquered the island in 1235 CE, Ibiza (Eivissa) had already been influenced by several cultures, starting with the Phoenicians, then the Carthaginians, followed by the Umayyads. The impact of these various cultures on the genetic structure of the islanders is still unexplored. Our results show a clear distinction between Ibiza and the rest of Spain. To investigate whether this was due to the Phoenician colonization or to more recent events, we compared the genomes of current Ibizans to that of an ancient Phoenician sample from Ibiza and to both modern Levantine and North African genomes. We did not identify any trace of Phoenician ancestry in the current Ibizans. Interestingly, the analysis of runs of homozygosity and changes in the effective population size through time support the idea that drift has shaped the genetic structure of current Ibizans. In addition to the small carrying capacity of the island, Ibiza experienced a series of dramatic demographic changes due to several instances of famine, war, malaria and plague that could have significantly contributed to its current genetic differentiation.

9.
Bioinformatics ; 35(11): 1916-1922, 2019 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-30351417

RESUMEN

MOTIVATION: Data processing is a key bottleneck for 1H NMR-based metabolic profiling of complex biological mixtures, such as biofluids. These spectra typically contain several thousands of signals, corresponding to possibly few hundreds of metabolites. A number of binning-based methods have been proposed to reduce the dimensionality of 1 D 1H NMR datasets, including statistical recoupling of variables (SRV). Here, we introduce a new binning method, named JBA ("pJRES Binning Algorithm"), which aims to extend the applicability of SRV to pJRES spectra. RESULTS: The performance of JBA is comprehensively evaluated using 617 plasma 1H NMR spectra from the FGENTCARD cohort. The results presented here show that JBA exhibits higher sensitivity than SRV to detect peaks from low-abundance metabolites. In addition, JBA allows a more efficient removal of spectral variables corresponding to pure electronic noise, and this has a positive impact on multivariate model building. AVAILABILITY AND IMPLEMENTATION: The algorithm is implemented using the MWASTools R/Bioconductor package. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

10.
Sci Rep ; 8(1): 17567, 2018 12 04.
Artículo en Inglés | MEDLINE | ID: mdl-30514893

RESUMEN

Ibiza was permanently settled around the 7th century BCE by founders arriving from west Phoenicia. The founding population grew significantly and reached its height during the 4th century BCE. We obtained nine complete mitochondrial genomes from skeletal remains from two Punic necropoli in Ibiza and a Bronze Age site from Formentara. We also obtained low coverage (0.47X average depth) of the genome of one individual, directly dated to 361-178 cal BCE, from the Cas Molí site on Ibiza. We analysed and compared ancient DNA results with 18 new mitochondrial genomes from modern Ibizans to determine the ancestry of the founders of Ibiza. The mitochondrial results indicate a predominantly recent European maternal ancestry for the current Ibizan population while the whole genome data suggest a significant Eastern Mediterranean component. Our mitochondrial results suggest a genetic discontinuity between the early Phoenician settlers and the island's modern inhabitants. Our data, while limited, suggest that the Eastern or North African influence in the Punic population of Ibiza was primarily male dominated.


Asunto(s)
Grupo de Ascendencia Continental Africana/historia , ADN Antiguo , Emigración e Inmigración/historia , Grupo de Ascendencia Continental Europea/historia , Grupo de Ascendencia Continental Africana/genética , Arqueología , Restos Mortales , ADN Mitocondrial/genética , Grupo de Ascendencia Continental Europea/genética , Variación Genética , Genoma Mitocondrial/genética , Historia Antigua , Humanos , Masculino , Filogeografía , España
11.
Ann Hum Biol ; 45(1): 98-104, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29382280

RESUMEN

BACKGROUND: The genetic composition of human North African populations is an amalgam of different ancestral components coming from the Middle East, Europe, south-Saharan Africa and autochthonous to North Africa. This complex genetic pattern is the result of migrations and admixtures in the region since Palaeolithic times. AIMS: The objective of the present study is to refine knowledge of the population history of North African populations through the analysis of complete mitochondrial sequences. SUBJECTS AND METHODS: This study has sequenced complete mitochondrial DNAs (mtDNAs) in several North African and neighbouring individuals. RESULTS: The mtDNA haplogroup classification and phylogeny shows a high genetic diversity in the region as a result of continuous admixture. The phylogenetic analysis allowed us to identify a new haplogroup characterised by positions 10 101 C and 146 C (H1v2), a sub-branch of H1v, which is restricted to North Africa and whose origins are estimated as ∼4000 years ago. CONCLUSIONS: The analysis of the complete mtDNA genome has allowed for the identification of a North African sub-lineage that might be ignored by the analysis of partial mtDNA control region sequences, highlighting the phylogeographic relevance of mtDNA complete sequence analysis.


Asunto(s)
ADN Mitocondrial/genética , Variación Genética , Haplotipos , Filogenia , África del Norte , Humanos , Filogeografía , Secuenciación Completa del Genoma
13.
Emerg Infect Dis ; 24(2): 374-376, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29350169

RESUMEN

A preparedness plan for avian influenza A(H5N1) virus infection was activated in Lebanon in 2016 after reported cases in poultry. Exposed persons were given prophylaxis and monitored daily. A total of 185 exposed persons were identified: 180 received prophylaxis, 181 were monitored, and 41 suspected cases were reported. All collected specimens were negative for virus by PCR.


Asunto(s)
Pollos , Brotes de Enfermedades/veterinaria , Subtipo H5N1 del Virus de la Influenza A/aislamiento & purificación , Gripe Aviar/virología , Gripe Humana/epidemiología , Gripe Humana/virología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Animales , Antivirales/uso terapéutico , Niño , Preescolar , Femenino , Humanos , Lactante , Gripe Aviar/epidemiología , Gripe Humana/tratamiento farmacológico , Gripe Humana/prevención & control , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Oseltamivir/uso terapéutico , Adulto Joven
14.
Influenza Other Respir Viruses ; 12(3): 331-335, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29152890

RESUMEN

BACKGROUND: Given the sparse information on the burden of influenza in Lebanon, the Ministry of Public Health established a sentinel surveillance for severe acute respiratory infections (SARI) to identify the attribution of influenza to reported cases. We aim to highlight the proportion of influenza-associated SARI from September 1st, 2015 to August 31st, 2016 in 2 Lebanese hospitals. METHODS: The study was conducted in 2 sentinel sites located in Beirut suburbs and southern province of Lebanon. WHO's 2011 standardized SARI case definition was used. Data from September 1, 2015 to August 31, 2016 were reviewed, and all-cause hospital admission numbers were obtained. Nasopharyngeal swabs were collected and tested by RT-PCR. Descriptive and bivariate analyses were conducted using STATA 13. RESULTS: The 2 sentinel sites reported 746 SARI cases during the studied time frame: 467 from the southern province site and 279 from the Beirut suburbs site. SARI reports peaked between January and March 2016. All, except 4, cases were sampled, and a co-dominance of influenza B (43%) and influenza A (H1N1) (41%) was evident. A high proportion of cases was reported in children <2 years 274 (37%). The proportional contribution of influenza-associated SARI to all-cause hospital admissions was high in children <2 years in the south (4.5% [95% CI: 3.1-6.5]) and in children <5 years in Beirut (0.7% [95% CI: 0.6-0.8]). CONCLUSION: This is the first study to highlight the proportion of influenza-associated SARI in 2 hospitals in Lebanon. The findings will be beneficial for supporting respiratory prevention and immunization program policies.


Asunto(s)
Hospitalización/estadística & datos numéricos , Gripe Humana/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Vigilancia de Guardia , Enfermedad Aguda/epidemiología , Adolescente , Adulto , Anciano , Niño , Preescolar , Costo de Enfermedad , Femenino , Humanos , Lactante , Subtipo H1N1 del Virus de la Influenza A , Subtipo H3N2 del Virus de la Influenza A , Gripe Humana/prevención & control , Líbano/epidemiología , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Proyectos Piloto , Infecciones del Sistema Respiratorio/virología , Adulto Joven
15.
Sci Rep ; 7(1): 15941, 2017 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-29162904

RESUMEN

E-M183 (E-M81) is the most frequent paternal lineage in North Africa and thus it must be considered to explore past historical and demographical processes. Here, by using whole Y chromosome sequences from 32 North African individuals, we have identified five new branches within E-M183. The validation of these variants in more than 200 North African samples, from which we also have information of 13 Y-STRs, has revealed a strong resemblance among E-M183 Y-STR haplotypes that pointed to a rapid expansion of this haplogroup. Moreover, for the first time, by using both SNP and STR data, we have provided updated estimates of the times-to-the-most-recent-common-ancestor (TMRCA) for E-M183, which evidenced an extremely recent origin of this haplogroup (2,000-3,000 ya). Our results also showed a lack of population structure within the E-M183 branch, which could be explained by the recent and rapid expansion of this haplogroup. In spite of a reduction in STR heterozygosity towards the West, which would point to an origin in the Near East, ancient DNA evidence together with our TMRCA estimates point to a local origin of E-M183 in NW Africa.


Asunto(s)
Grupo de Ascendencia Continental Africana/genética , Cromosomas Humanos Y/genética , Filogenia , África del Norte , Secuencia de Bases , Teorema de Bayes , Haplotipos/genética , Humanos , Masculino , Repeticiones de Microsatélite/genética , Polimorfismo de Nucleótido Simple/genética , Análisis de Componente Principal , Factores de Tiempo
16.
Genes (Basel) ; 8(11)2017 Nov 07.
Artículo en Inglés | MEDLINE | ID: mdl-29112131

RESUMEN

Monogenic forms of diabetes may account for 1-5% of all cases of diabetes, and may occur in the context of syndromic presentations. We investigated the case of a girl affected by insulin-dependent diabetes, diagnosed at 6 years old, associated with congenital cataract. Her consanguineous parents and her four other siblings did not have diabetes or cataract, suggesting a recessive syndrome. Using whole exome sequencing of the affected proband, we identified a heterozygous p.R825Q ABCC8 mutation, located at the exact same amino-acid position as the p.R825W recurring diabetes mutation, hence likely responsible for the diabetes condition, and a homozygous p.G71S mutation in CRYBB1, a gene known to be responsible for congenital cataract. Both mutations were predicted to be damaging and were absent or extremely rare in public databases. Unexpectedly, we found that the mother was also homozygous for the CRYBB1 mutation, and both the mother and one unaffected sibling were heterozygous for the ABCC8 mutation, suggesting incomplete penetrance of both mutations. Incomplete penetrance of ABCC8 mutations is well documented, but this is the first report of an incomplete penetrance of a CRYBB1 mutation, manifesting between susceptible subjects (unaffected mother vs. affected child) and to some extent within the patient herself, who had distinct cataract severities in both eyes. Our finding illustrates the importance of family studies to unmask the role of confounding factors such as double-gene mutations and incomplete penetrance that may mimic monogenic syndromes including in the case of strongly evocative family structure with consanguinity.

17.
Inhal Toxicol ; 29(10): 429-434, 2017 08.
Artículo en Inglés | MEDLINE | ID: mdl-29064301

RESUMEN

BACKGROUND: Waterpipe smoking is a rising global public health epidemic perceived by many users to be less harmful, though its toxicity overlaps or even exceeds that of cigarette smoking. Short-term cardiovascular changes due to waterpipe smoking are well established, but longer-term health impacts are still not fully elucidated. OBJECTIVE: We aim to investigate the association of waterpipe smoking with myocardial infarction among patients undergoing cardiac catheterization. METHODS: The study was performed on Lebanese patients referred for cardiac catheterization. Patient's blood was collected for metabolic measures and questionnaires were filled out to include socio-demographic, behavioral and pertinent medical characteristics of the study subjects. RESULTS: Myocardial infarction is significantly and independently associated with waterpipe smoking, with odds ratio (OR) of 1.329 (95% CI: [1.04-1.68]; p = .021), which is lower than that for cigarette smoking (OR = 1.87, 95% CI: [1.63-2.15]; p < .001). Only diabetes showed significant association with waterpipe smoking among MI enrollees (OR = 1.66, 95%CI: [1.04-2.63]; p = .032). CONCLUSION: The study provides yet another evidence for the adverse cardiovascular effects of waterpipe smoking on a clinical level. The harmful effects of waterpipe smoking should be underscored by health care professionals.


Asunto(s)
Cateterismo Cardíaco , Síndrome Metabólico/etiología , Infarto del Miocardio/etiología , Fumar en Pipa de Agua/efectos adversos , Anciano , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/etiología , Femenino , Humanos , Líbano/epidemiología , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Encuestas y Cuestionarios
18.
Anal Chem ; 89(21): 11405-11412, 2017 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-28937204

RESUMEN

1H nuclear magnetic resonance (NMR) spectroscopy-based metabolic phenotyping is now widely used for large-scale epidemiological applications. To minimize signal overlap present in 1D 1H NMR spectra, we have investigated the use of 2D J-resolved (JRES) 1H NMR spectroscopy for large-scale phenotyping studies. In particular, we have evaluated the use of the 1D projections of the 2D JRES spectra (pJRES), which provide single peaks for each of the J-coupled multiplets, using 705 human plasma samples from the FGENTCARD cohort. On the basis of the assessment of several objective analytical criteria (spectral dispersion, attenuation of macromolecular signals, cross-spectral correlation with GC-MS metabolites, analytical reproducibility and biomarker discovery potential), we concluded that the pJRES approach exhibits suitable properties for implementation in large-scale molecular epidemiology workflows.


Asunto(s)
Metabolómica/métodos , Fenotipo , Plasma/metabolismo , Espectroscopía de Protones por Resonancia Magnética , Femenino , Humanos , Masculino , Flujo de Trabajo
19.
Am J Hum Genet ; 101(2): 274-282, 2017 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-28757201

RESUMEN

The Canaanites inhabited the Levant region during the Bronze Age and established a culture that became influential in the Near East and beyond. However, the Canaanites, unlike most other ancient Near Easterners of this period, left few surviving textual records and thus their origin and relationship to ancient and present-day populations remain unclear. In this study, we sequenced five whole genomes from ∼3,700-year-old individuals from the city of Sidon, a major Canaanite city-state on the Eastern Mediterranean coast. We also sequenced the genomes of 99 individuals from present-day Lebanon to catalog modern Levantine genetic diversity. We find that a Bronze Age Canaanite-related ancestry was widespread in the region, shared among urban populations inhabiting the coast (Sidon) and inland populations (Jordan) who likely lived in farming societies or were pastoral nomads. This Canaanite-related ancestry derived from mixture between local Neolithic populations and eastern migrants genetically related to Chalcolithic Iranians. We estimate, using linkage-disequilibrium decay patterns, that admixture occurred 6,600-3,550 years ago, coinciding with recorded massive population movements in Mesopotamia during the mid-Holocene. We show that present-day Lebanese derive most of their ancestry from a Canaanite-related population, which therefore implies substantial genetic continuity in the Levant since at least the Bronze Age. In addition, we find Eurasian ancestry in the Lebanese not present in Bronze Age or earlier Levantines. We estimate that this Eurasian ancestry arrived in the Levant around 3,750-2,170 years ago during a period of successive conquests by distant populations.


Asunto(s)
ADN Mitocondrial/genética , Grupos Étnicos/genética , Genética de Población/métodos , Genoma Humano/genética , Grupo de Ascendencia Continental Europea/genética , Variación Genética/genética , Historia Antigua , Humanos , Líbano , Desequilibrio de Ligamiento , Masculino
20.
Nat Genet ; 49(9): 1385-1391, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28714975

RESUMEN

Genome-wide association studies (GWAS) in coronary artery disease (CAD) had identified 66 loci at 'genome-wide significance' (P < 5 × 10-8) at the time of this analysis, but a much larger number of putative loci at a false discovery rate (FDR) of 5% (refs. 1,2,3,4). Here we leverage an interim release of UK Biobank (UKBB) data to evaluate the validity of the FDR approach. We tested a CAD phenotype inclusive of angina (SOFT; ncases = 10,801) as well as a stricter definition without angina (HARD; ncases = 6,482) and selected cases with the former phenotype to conduct a meta-analysis using the two most recent CAD GWAS. This approach identified 13 new loci at genome-wide significance, 12 of which were on our previous list of loci meeting the 5% FDR threshold, thus providing strong support that the remaining loci identified by FDR represent genuine signals. The 304 independent variants associated at 5% FDR in this study explain 21.2% of CAD heritability and identify 243 loci that implicate pathways in blood vessel morphogenesis as well as lipid metabolism, nitric oxide signaling and inflammation.


Asunto(s)
Enfermedad de la Arteria Coronaria/genética , Sitios Genéticos/genética , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo/métodos , Estudios de Asociación Genética/métodos , Estudios de Asociación Genética/normas , Estudios de Asociación Genética/estadística & datos numéricos , Estudio de Asociación del Genoma Completo/normas , Estudio de Asociación del Genoma Completo/estadística & datos numéricos , Genotipo , Sistemas de Información en Salud/normas , Sistemas de Información en Salud/estadística & datos numéricos , Humanos , Metaanálisis como Asunto , Fenotipo , Polimorfismo de Nucleótido Simple , Reproducibilidad de los Resultados , Factores de Riesgo , Reino Unido
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