Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders1. They are heritable2,3 and etiologically related4,5 behaviors that have been resistant to gene discovery efforts6-11. In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use

Tobacco and alcohol use are leading causes of mortality that influence risk for many complex diseases and disorders 1 . They are heritable 2,3 and etiologically related 4,5 behaviors that have been resistant to gene discovery efforts 6–11 . In sample sizes up to 1.2 million individuals, we discovered 566 genetic variants in 406 loci associated with multiple stages of tobacco use (initiation, cessation, and heaviness) as well as alcohol use, with 150 loci evidencing pleiotropic association. Smoking phenotypes were positively genetically correlated with many health conditions, whereas alcohol use was negatively correlated with these conditions, such that increased genetic risk for alcohol use is associated with lower disease risk. We report evidence for the involvement of many systems in tobacco and alcohol use, including genes involved in nicotinic, dopaminergic, and glutamatergic neurotransmission. The results provide a solid starting point to evaluate the effects of these loci in model organisms and more precise substance use measures

Assimilation and partial melting of continental crust: evidence from the mineralogy and geochemistry of autoliths and xenoliths

This paper presents a model for the partial melting of quartz diorite and greywacke in the upper crust based on the mineralogy and geochemistry of enclaves within the Loch Doon granitic intrusion of southern Scotland. The melting of quartz diorite was modelled using autoliths, which represent fragments of cogenetic igneous rocks that became incorporated in the fractionating magma. Compared to their quartz diorite parents, the autoliths are enriched to varying degrees in some elements (notably Rb, Nb, Ta, Sm, Y, Yb) and depleted in others (Sr, and Ba); Eu and P are also depleted in the more assimitated autoliths. The compositions of melts that could be derived from assimilation of the autoliths have also been calculated: their REE patterns reveal a light REE enrichment, low concentrations of heavy REEs (1–3 x chondrite) and a positive Eu anomaly. The calculated degrees of melting vary from 35% in the least assimilated to 84% in the most assimilated autolith (assuming a bulk distribution coefficient of 10 for the most compatible element). Results from modelling of xenolith compositions (derived from metasediments) are also reported, but because of uncertainties in the composition of the parental sediment, these data are subject to larger errors. They do, however, indicate that resultant partial melts are distinctly different from those derived by partial melting of autoliths. In particular, the REE pattern of a greywacke-derived melt shows a slight enrichment in light REEs, greater concentrations of heavy REEs (10 x chondrite) and a small negative Eu anomaly. The calculated degrees of melting of the xenoliths fall in the range of 66–88% (assuming a bulk distribution coefficient of 10 for the most compatible element). The results have direct implications for assimilation and melting of the upper crust. By taking into account how the nature of residual phases is likely to change with depth, it can be demonstrated that some Archaean tonalite gneisses could represent liquids derived by partial melting of igneous material

Petrogenetic modelling of in situ fractional crystallization in the zoned Loch Doon pluton, Scotland

The late Caledonian Loch Doon granitic intrusion ranges in composition from hypersthene diorite at the margin, through quartz diorite, granodiorite and granite to cordierite microgranite at its core. Petrogenetic modelling of trace element variations and least squares analysis of major elements indicate that two distinct magmas are involved, each magma controlled by crystallization of plag-opx-cpx-bio. Late stage rocks related to the second magma include the cordierite microgranites and aplites, which are interpreted as the final residue which crystallized rapidly after a build up and loss of volatiles. Analyses of whole rocks and minerals for REE's and other elements of moderate-high ionic potential indicate that these elements are strongly controlled by minor phase crystallization; apatite, zircon, sphene and allanite are dominant at intermediate compositions but other accessory minerals such as monazite and xenotime may also become important at acid compositions. It is probable that within each magma the mechanisms of crystal settling and filter pressing operated, the former being initially dominant, and the latter becoming more important with increasing degree of fractional crystallization

Oxide minerals of the Separation Rapids rare-element granitic pegmatite group, northwestern Ontario

The newly discovered Separation Rapids pegmatite group, situated in mafic metavolcanic host-rocks that represent the eastern extremity of the Bird River metavolcanic-metasedimentary belt, contains Ontario's first occurrences of wodginite-group minerals (mainly wodginite and ferrowodginite), the pyrochlore-group minerals stibiomicrolite, stibiobetafite and yttropyrochlore, ferrotapiolite, and probably the first occurrence in North America of nigerite from a granitic pegmatite. This example of the rare-element class of granitic pegmatites hosts both beryl- and petalite-subtype pegmatites. Columbite-tantalite and cassiterite are the predominant oxide species. On the basis of columbite-tantalite compositions, the pegmatites have been divided into an Fe-suite and a Mn-suite. Both beryl and petalite pegmatites occur in each suite. On the basis of ferrocolumbite compositions, the associated Separation Rapids pluton is considered to be the parent of at least the Fe-suite of pegmatites. The Fe suite includes beryl pegmatites within and adjacent to the pluton, in which ferrocolumbite coexists with ferrowodginite, and, with increasing evolution, petalite-bearing pegmatites that contain ferrotantalite and wodginite. In individual pegmatites, columbite-tantalite variation is mainly in Ta/(Ta+Nb). Minor microlite, antimonian microlite and stibiomicrolite are found replacing earlier phases. Cassiterite is the final Nb-Ta-bearing oxide to crystallize. Pegmatites belonging to the Mn-suite follow a similar pattern of crystallization, with early manganocolumbite followed by manganotantalite, the latter coexisting with wodginite. Manganocolumbite within individual samples varies appreciably in Mn/(Mn+Fe), whereas the variation in manganotantalite is mainly in Ta/(Ta+Nb). In pods rich in "cleavelandite" and Li-mica within one of the beryl pegmatites, extreme Mn-enrichment has produced near-end-member manganotantalite and W-bearing wodginite. Microlite is an important late phase, which is either primary or forms as a replacement, mainly of wodginite. The presence of microlite, lithian mica and topaz in Mn-suite pegmatites (and aplites) indicates that they were derived from a more F-rich melt than that which produced the Fe-suite of pegmatites. Albitization also is more apparent in the Mn-suite of pegmatites. The wall zone of Marko's pegmatite, the largest body in the eastern subgroup and part of the Mn-suite, is unique in hosting titanowodginite, "ferrotitanowodginite", stibiobetafite and struverite. These Fe-, Ti- and Sb-phases are considered to have developed as a result of interaction of the pegmatite-forming melt with banded ironstones and Fe-Ti-rich metavolcanic host-rocks

Algodonite and domeykite from New Cliffe Hill quarry, Stanton-under-Bardon, Leicestershire

The main copper assemblage found at New Cliffe Hill Quarry comprises major amounts of cuprite, copper and malachite. Other minerals are uncommon but include trace amounts of silver, tenorite, the copper sulphides chalcocite/djurleite, yarrowite and the rare copper-arsenic species algodonite and domeykite. Analyses of domeykite (Cu2.99As) show it to be close to its stoichiometric formula Cu3As but algodonite has a range of compositions from Cu5.39As to Cu6.07As. This paper presents the first analyses of algodonite in Britain that are close to its stoichiometric formula. A minor sulphide assemblage from New Cliffe Hill Quarry carries chalcopyrite, bornite, ‘chalcocite’, spionkopite, yarrowite and covelline and in many respects has a similar petrography to the sulphide assemblage seen at Judkins Quarry where bornite (and its alteration product ‘idaite’), chalcopyrite, minor tetrahedrite, trace amounts of possible cobaltite and blue copper sulphides including geerite, djurleite, digenite, spionkopite and yarrowite occur. An origin for the copper from Permo-Triassic red beds rather than spatially associated Precambrian igneous rocks is favoure

The first British occurrence of arsenogoyazite at Wheal Cock, St Just, Cornwall

Arsenogoyazite occurs as opaque white pseudo-cubic crystals in cavities in quartz veinstone collected from the dumps at Wheal Cock, St Just, Cornwall. The crystals show complex chemical substitutions. They are fluoride, sulphate and phosphate-rich and contain significant calcium and barium. This is the first report of arsenogoyazite in the British Isles

The first British occurrence of philipsbornite at Wheal Unity, Gwennap, Cornwall

The rare supergene mineral philipsbornite has been identified at Wheal Unity, Gwennap, Cornwall. It occurs in drusy crusts composed of minute trigonal crystals. Empirical formulae determined for two typical grains are in good agreement with theoretical expectations for members of the crandallite group. Iron, sulphate, phosphate and fluoride are the major chemical substitutions