Multiple Independent Genetic Factors at NOS1AP Modulate the QT Interval in a Multi-Ethnic Population

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6×10−5) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP × sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63×10−8), as well as the sex-interaction with rs16847548 (P = 8.68×10−6). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval

Neoproterozoic to early Paleozoic extensional and compressional history of East Laurentian margin sequences: The Moine Supergroup, Scottish Caledonides

Neoproterozoic siliciclastic-dominated sequences are widespread along the eastern margin of Laurentia and are related to rifting associated with the breakout of Laurentia from the supercontinent Rodinia. Detrital zircons from the Moine Supergroup, NW Scotland, yield Archean to early Neoproterozoic U-Pb ages, consistent with derivation from the Grenville-Sveconorwegian orogen and environs and accumulation post–1000 Ma. U-Pb zircon ages for felsic and associated mafic intrusions confirm a widespread pulse of extension-related magmatism at around 870 Ma. Pegmatites yielding U-Pb zircon ages between 830 Ma and 745 Ma constrain a series of deformation and metamorphic pulses related to Knoydartian orogenesis of the host Moinerocks. Additional U-Pb zircon and monazite data, and 40Ar/39Ar ages for pegmatites and host gneisses indicate high-grade metamorphic events at ca. 458–446 Ma and ca. 426 Maduring the Caledonian orogenic cycle.The presence of early Neoproterozoic silici clastic sedimentation and deformation in the Moine and equivalent successions around the North Atlantic and their absence along strike in eastern North America reflect contrasting Laurentian paleogeography during the breakup of Rodinia. The North Atlantic realm occupied an external location on the margin of Laurentia, and this region acted as a locus for accumulation of detritus (Moine Supergroup and equivalents) derived from the Grenville-Sveconorwegian orogenic welt, which developed as a consequence of collisional assembly of Rodinia. Neoproterozoic orogenic activity corresponds with theinferred development of convergent platemargin activity along the periphery of the supercontinent. In contrast in eastern North America, which lay within the internal parts of Rodinia, sedimentation did not commence until the mid-Neoproterozoic (ca. 760 Ma) during initial stages of supercontinent fragmentation. In the North Atlantic region, this time frame corresponds to a second pulse of extension represented by units such as the Dalradian Supergroup, which unconformably overlies the predeformed Moine succession

Palaeomagnetic configuration of continents during the Proterozoic

Palaeomagnetic data are used to study the configurations of continents during the Proterozoic. Applying stringent reliability criteria, the positions of the continents at 12 times in the 2.45- to 1.00-Ga period have been constructed. The continents lie predominantly in low to intermediate latitudes. The sedimentological indicators of palaeoclimate are generally consistent with the palaeomagnetic latitudes, with the exception of the Early Proterozoic, when low latitude glaciations took place on several continents. The Proterozoic continental configurations are generally in agreement with current geological models of the evolution of the continents. The data suggest that three large continental landmasses existed during the Proterozoic. The oldest one is the Neoarchaean Kenorland, which comprised at least Laurentia, Baltica, Australia and the Kalahari craton. The protracted breakup of Kenorland during the 2.45- to 2.10-Ga interval is manifested by mafic dykes and sedimentary rift-basins on many continents. The second 'supercontinental' landmass is Hudsonland (also known as Columbia). On the basis of purely palaeomagnetic data, this supercontinent consisted of Laurentia, Baltica, Ukraine, Amazonia and Australia and perhaps also Siberia, North China and Kalahari. Hudsonland existed from 1.83 to ca. 1.50-1.25 Ga. The youngest assembly is the Neoproterozoic supercontinent of Rodinia, which was formed by continent-continent collisions during similar to 1.10-1.00 Ga and which involved most of the continents. A new model for its assembly and configuration is presented, which suggests that multiple Grenvillian age collisions took place during 1.10-1.00 Ga. The configurations of Kenorland, Hudsonland and Rodinia depart from each other and also from the Pangaea assembly. The tectonic styles of their amalgamation are also different reflecting probable changes in sizes and thicknesses of the cratonic blocks as well as changes in the thermal conditions of the mantle through time. (C) 2003 Elsevier B.V. All rights reserved