Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (∼50% of these regions have multiple independent associations); these include 24 novel SLE regions (P<5 × 10-8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SLE.info:eu-repo/semantics/publishedVersio

Transancestral mapping and genetic load in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease with marked gender and ethnic disparities. We report a large transancestral association study of SLE using Immunochip genotype data from 27,574 individuals of European (EA), African (AA) and Hispanic Amerindian (HA) ancestry. We identify 58 distinct non-HLA regions in EA, 9 in AA and 16 in HA (B50% of these regions have multiple independent associations); these include 24 novel SLE regions (Po5 10 8), refined association signals in established regions, extended associations to additional ancestries, and a disentangled complex HLA multigenic effect. The risk allele count (genetic load) exhibits an accelerating pattern of SLE risk, leading us to posit a cumulative hit hypothesis for autoimmune disease. Comparing results across the three ancestries identifies both ancestry-dependent and ancestry-independent contributions to SLE risk. Our results are consistent with the unique and complex histories of the populations sampled, and collectively help clarify the genetic architecture and ethnic disparities in SL

Long-term droughts may drive drier tropical forests towards increased functional, taxonomic and phylogenetic homogeneity

Tropical ecosystems adapted to high water availability may be highly impacted by climatic changes that increase soil and atmospheric moisture deficits. Many tropical regions are experiencing significant changes in climatic conditions, which may induce strong shifts in taxonomic, functional and phylogenetic diversity of forest communities. However, it remains unclear if and to what extent tropical forests are shifting in these facets of diversity along climatic gradients in response to climate change. Here, we show that changes in climate affected all three facets of diversity in West Africa in recent decades. Taxonomic and functional diversity increased in wetter forests but tended to decrease in forests with drier climate. Phylogenetic diversity showed a large decrease along a wet-dry climatic gradient. Notably, we find that all three facets of diversity tended to be higher in wetter forests. Drier forests showed functional, taxonomic and phylogenetic homogenization. Understanding how different facets of diversity respond to a changing environment across climatic gradients is essential for effective long-term conservation of tropical forest ecosystems

Geochemical and isotopic variability controlled by slab detachment in a subduction zone with varying dip: the Eastern Trans-Mexican Volcanic Belt

Strong compositional variations are observed in the late-Miocene to Quaternary volcanic rocks of the eastern Trans-Mexican Volcanic Belt. Geochemical and isotopic analyses of samples well constrained in age indicate an abrupt change in magma composition in the late-Miocene (not, vert, similar 7.5 Ma), when calc-alkaline, subduction-related magmatism was replaced by mafic, alkaline, OIB-like volcanism. Afterwards, volcanism migrated toward the trench and the erupted lavas showed increasing contributions of subduction components reflected in higher Th/Nb, La/Sm(n), Ba/Nb, and Ba/Th ratios. Lavas from volcanic fields located closer to the trench show clearer, although strongly variable, arc signatures as well as evidence of subducted sediment contributions. Farther from the trench, only lavas emplaced in late-Pliocene time appear to be slightly modified by subduction components, whereas the youngest Quaternary lavas can be regarded as intraplate lavas modified by crustal assimilation. The sudden change in magma composition in the late-Miocene is related to detachment of the subducting slab, which allowed the infiltration of enriched asthenospheric mantle into the mantle wedge. After detachment, the subducting plate started to increase its dip because of the loss of slab pull. This caused (1) the migration of the arc toward the trench, (2) convection of enriched asthenosphere into the mantle wedge, and (3) an increasing contribution of slab components to the melts, in a process that resulted in a highly heterogeneous source mantle. The variable contribution of subduction-related components to the magmas is controlled by the heterogeneous character of the source, the depth of the subducting plate, and the previous magmatic history of the areas

Geochemical and isotopic variability controlled by slab detachment in a subduction zone with varying dip: the Eastern Trans-Mexican Volcanic Belt

Strong compositional variations are observed in the late-Miocene to Quaternary volcanic rocks of the eastern Trans-Mexican Volcanic Belt. Geochemical and isotopic analyses of samples well constrained in age indicate an abrupt change in magma composition in the late-Miocene (not, vert, similar 7.5 Ma), when calc-alkaline, subduction-related magmatism was replaced by mafic, alkaline, OIB-like volcanism. Afterwards, volcanism migrated toward the trench and the erupted lavas showed increasing contributions of subduction components reflected in higher Th/Nb, La/Sm(n), Ba/Nb, and Ba/Th ratios. Lavas from volcanic fields located closer to the trench show clearer, although strongly variable, arc signatures as well as evidence of subducted sediment contributions. Farther from the trench, only lavas emplaced in late-Pliocene time appear to be slightly modified by subduction components, whereas the youngest Quaternary lavas can be regarded as intraplate lavas modified by crustal assimilation.\ud \ud The sudden change in magma composition in the late-Miocene is related to detachment of the subducting slab, which allowed the infiltration of enriched asthenospheric mantle into the mantle wedge. After detachment, the subducting plate started to increase its dip because of the loss of slab pull. This caused (1) the migration of the arc toward the trench, (2) convection of enriched asthenosphere into the mantle wedge, and (3) an increasing contribution of slab components to the melts, in a process that resulted in a highly heterogeneous source mantle. The variable contribution of subduction-related components to the magmas is controlled by the heterogeneous character of the source, the depth of the subducting plate, and the previous magmatic history of the areas

Geology, geochronology and tectonic setting of late Cenozoic volcanism along the southwestern Gulf of Mexico: The Eastern Alkaline Province revisited

A NNW-trending belt of alkaline mafic volcanic fields parallels the Gulf of Mexico from the U.S. border southward to Veracruz state, in eastern Mexico. Previous studies grouped this volcanism into the so-called “Eastern Alkaline Province” (EAP) and suggested that it resulted from Gulf-parallel extensional faulting migrating from north to south from Oligocene to Present. On the basis of new geologic studies, forty-nine unspiked K–Ar and two 40Ar–39Ar ages, we propose a new geodynamic model for the volcanism along the southwestern Gulf of Mexico. We studied in detail four of the six recognized fields of mafic alkaline volcanism in Veracruz state: 1) The lavas flows of Tlanchinol area (7.3–5.7 Ma), 2) the Alamo monogenetic field and Sierra de Tantima (7.6–6.6 Ma), 3) the Poza Rica and Metlatoyuca lava flows (1.6–1.3 Ma) and 4) the Chiconquiaco–Palma Sola area (6.9–3.2 Ma). Other two mafic volcanic fields may represent the continuation of alkaline volcanism to the southeast: the Middle Miocene lavas at Anegada High, offshore port of Veracruz, and the Middle to Late Miocene volcanism at the Los Tuxtlas. The existence of major Neogene extensional faults parallel to the Gulf of Mexico (i.e., not, vert, similarN–S to NNW–SSE) proposed in previous works was not confirmed by our geological studies. Elongation of volcanic necks, vent alignment, and faults mapped by subsurface data trend dominantly NE to ENE and NW to NNW. These directions are parallel to transform and normal faults that formed during the Late Jurassic opening of the Gulf of Mexico. Ascent of mafic magmas was likely facilitated and controlled by the existence of these pre-existing basement structures. Coupled with previous studies, our data demonstrate the occurrence of three magmatic episodes in Veracruz: 1) A Middle Miocene (not, vert, similar15–11 Ma) episode in southern Veracruz (Palma Sola, Anegada, and Los Tuxtlas); 2) A Late Miocene to Early Pliocene (not, vert, similar7.5–3 Ma) pulse of mafic alkaline volcanism throughout the study region; and 3) A Late Pliocene to Quaternary transitional to calc–alkaline volcanism in southern Veracruz (Palma Sola, Los Tuxtlas). Whereas the first and third episodes may be considered part of the subduction-related Trans-Mexican Volcanic Belt, the second pulse of mafic alkaline volcanism has a more complex origin. The absence of significant extensional faulting precludes a rift origin. We favor a model in which a transient thermal anomaly and melting of the mantle was triggered by the tearing and detachment of part of the subducted slab

Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

OBJECTIVES: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a strong genetic component. Our aim was to perform the first genome-wide association study on individuals from the Americas enriched for Native American heritage. MATERIALS AND METHODS: We analyzed 3,710 individuals from four countries of Latin America and the Unites States diagnosed with SLE and healthy controls. Samples were genotyped with the HumanOmni1 BeadChip. Data of out-of-study controls was obtained for the HumanOmni2.5. Statistical analyses were performed using SNPTEST and SNPGWA. Data was adjusted for genomic control and FDR. Imputation was done using IMPUTE2, and HiBAG for classical HLA alleles. RESULTS: The IRF5-TNPO3 region showed the strongest association and largest odds ratio (OR) (rs10488631, P(gcadj) = 2.61×10(−29), OR = 2.12, 95% CI: 1.88–2.39) followed by the HLA class II on the DQA2-DQB1 loci (rs9275572, P(gcadj) = 1.11 × 10(−16), OR = 1.62, 95% CI: 1.46–1.80; rs9271366, P(gcadj)=6.46 × 10(−12), OR = 2.06, 95% CI: 1.71–2.50). Other known SLE loci associated were ITGAM, STAT4, TNIP1, NCF2 and IRAK1. We identified a novel locus on 10q24.33 (rs4917385, P(gcadj) =1.4×10(−8)) with a eQTL effect (P(eqtl)=8.0 × 10(−37) at USMG5/miR1307), and describe novel loci. We corroborate SLE-risk loci previously identified in European and Asians. Local ancestry estimation showed that HLA allele risk contribution is of European ancestral origin. Imputation of HLA alleles suggested that autochthonous Native American haplotypes provide protection. CONCLUSIONS: Our results show the insight gained by studying admixed populations to delineate the genetic architecture that underlies autoimmune and complex diseases