18 research outputs found

    Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci

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    Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations withP <5 x 10(-8)in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P <5 x 10(-8)) in the discovery samples. Ten novel SNVs, including rs12616219 nearTMEM182, were followed-up and five of them (rs462779 inREV3L, rs12780116 inCNNM2, rs1190736 inGPR101, rs11539157 inPJA1, and rs12616219 nearTMEM182) replicated at a Bonferroni significance threshold (P <4.5 x 10(-3)) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, inCCDC141and two low-frequency SNVs inCEP350andHDGFRP2. Functional follow-up implied that decreased expression ofREV3Lmay lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.Peer reviewe

    by L. Billi

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    The analysis of the singularity structure of some series arising in the conjugation theory of holomorphic maps is performed using the Pad&apos;e Approximants. The validity of P.A. is checked for functions whose analytic structure is known: one observes that the numerical results are extremely sensitive on errors due to the use of a finite precision; normal or double precision used in FORTRAN codes is in most cases not sufficient to perform a numerical analysis of the singularity structure. In order to have significant results at high orders all the computations were carried out using codes which allow to operate with a sufficiently large number of digits. The case of linearizable diffeomorphisms and of mappings tangent to the identity of (C; 0) was considered: P.A. of both the direct and the inverse conjugating functions of a quadratic map to its normal form were computed and a comparison was performed with analytical results when available. When the singularity pattern was unknown, the pol..

    Telemetric monitoring of fetal blood pressure and heart rate in the freely moving pregnant sheep: a feasibility study

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    Remote telemetric monitoring of fetal haemodynamics in pregnant sheep would allow unrestricted animal movement, minimize suffering and distress, and improve animal welfare, while enhancing the quality of data collected. This may also be useful in clinical practice following fetal surgery. Using an open fetal surgical technique at approximately two-thirds of gestation, we implanted the catheter of a D70-PCTP haemodynamic telemetric device (Data Sciences International, Tilburg, The Netherlands) into the carotid artery of the fetal sheep (n ¼ 4). The attached transmitter was secured to the posterior aspect of the maternal anterior abdominal wall. Two receivers, with a range of 1 m each, were sited in an 11 m2 sheep enclosure to maximize animal freedom while allowing continuous monitoring of the ewe. The receivers were connected by cable to a nearby computer. In the first two procedures, both fetuses died eight and 12 days after surgery, and the catheter tip was observed to be lying in the bicarotid trunk. In the next two procedures the catheter tip was threaded further upstream from the insertion point, in an attempt to reach the fetal aorta, and both fetuses survived until the scheduled postmortem examination at the end of pregnancy. After catheter implantation, fetal blood pressure (BP) and heart rate (HR) were successfully recorded continuously for seven days and then hourly per day for a further three weeks. The fetal BP and HR values were in the normal range for healthy sheep fetuses.PublishedN/
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