| 1. |
- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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| 2. |
- Ahlzén, Rolf, 1950-
(författare)
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Why should physicians read? : Understanding clinical judgement and its relation to literary experience
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Is literary experience of any practical relevance to the clinician? This is the overall question addressed by this investigation, which starts by tracing the historical roots of scientific medicine. These are found to be intimately linked to a form of rationality associated with the scientific revolution of the 17th century and with “modernity”. Medical practice, however, is dependent also on another form of rationality associated with what Stephen Toulmin calls “the epistemology of the biographical”. The very core of clinical medicine is shown to be the clinical encounter, an interpretive meeting where the illness experience is at the centre of attention. The physician can reach the goals of medicine only by developing clinical judgement. Clinical judgement is subjected to close analysis and is assumed to be intimately connected to the form of knowledge Aristotle called phronesis. In order to explore how literature – drama, novels, poetry – may be related to clinical judgement, a view of literature is presented that emphasizes literature as an invitation to the reader, to be met responsibly and responsively. Literature carries a potential for a widened experience, for a more nuanced perception of reality – and this potential is suggested to be ethically relevant to the practice of medicine. The “narrative rationality” of a literary text constitutes a complement to the rationality pervading scientific medicine. The final step in my analysis is a closer exploration of the potential of the literary text to contribute to the growth of clinical judgement, in relation to the challenges of everyday clinical work. Some of the conditions that may facilitate such growth are outlined, but it is also shown that full empirical evidence for the beneficial effects of reading on the clinician reader is beyond reach.
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| 3. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 4. |
- Meyers, Robert J, et al.
(författare)
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Reasons for entering treatment reported by initially treatment-resistant patients with substance use disorders
- 2014
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Ingår i: Cognitive Behaviour Therapy. - : Routledge. - 1650-6073 .- 1651-2316. ; 43:4, s. 299-309
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Tidskriftsartikel (refereegranskat)abstract
- Many individuals with substance use disorders are resistant to entering formal treatment, despite the negative consequences that plague their own lives and the lives of concerned significant others (CSOs). Community Reinforcement and Family Training (CRAFT) has been developed as an effective strategy for helping family members who are concerned about the alcohol/drug use of a loved one who refuses to seek treatment. The present study explored reasons and feelings that played a part in these resistant individuals' (identified patients [IPs]) decision to begin treatment. Written statements and feelings of 36 initially treatment-refusing IPs, who were engaged into treatment via their CRAFT-trained CSOs, were examined upon entering treatment. Self-report forms assessed three complementary domains about entering treatment: (1) feelings about coming for treatment, (2) important reasons for entering treatment, and (3) reasons for entering treatment narratives. It was shown that the occurrences of self-reported positive emotions and statements that expressed a positive wish for change outweighed negative feelings and statements. Although conceivably these CRAFT-exposed IPs may have provided different responses than other treatment-seeking populations, the current study's strong IP reports of positive feelings, reasons, and narrative statements regarding treatment entry nonetheless address potential concerns that treatment-refusing IPs might only enter treatment if felt coerced by family members and while experiencing salient negative feelings overall.
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