There is increasing evidence that genome-wide association (GWA) studies represent a powerful approach to the identification of genes involved in common human diseases. We describe a joint GWA study (using the Affymetrix GeneChip 500K Mapping Array Set) undertaken in the British population, which has examined approximately 2,000 individuals for each of 7 major diseases and a shared set of approximately 3,000 controls. Case-control comparisons identified 24 independent association signals at

BackgroundPatients’ beliefs about treatment influence treatment engagement and adherence. The Necessity-Concerns Framework postulates that adherence is influenced by implicit judgements of personal need for the treatment (necessity beliefs) and concerns about the potential adverse consequences of taking it.ObjectiveTo assess the utility of the NCF in explaining nonadherence to prescribed medicines.Data sourcesWe searched EMBASE, Medline, PsycInfo, CDSR/DARE/CCT and CINAHL from January 1999 to April 2013 and handsearched reference sections from relevant articles.Study eligibility criteriaStudies using the Beliefs about Medicines Questionnaire (BMQ) to examine perceptions of personal necessity for medication and concerns about potential adverse effects, in relation to a measure of adherence to medication.ParticipantsPatients with long-term conditions.Study appraisal and synthesis methodsSystematic review and meta-analysis of methodological quality was assessed by two independent reviewers. We pooled odds ratios for adherence using random effects models.ResultsWe identified 3777 studies, of which 94 (N = 25,072) fulfilled the inclusion criteria. Across studies, higher adherence was associated with stronger perceptions of necessity of treatment, OR = 1.742, 95% CI [1.569, 1.934], p<0.0001, and fewer Concerns about treatment, OR = 0.504, 95% CI: [0.450, 0.564], p<0.0001. These relationships remained significant when data were stratified by study size, the country in which the research was conducted and the type of adherence measure used.LimitationsFew prospective longitudinal studies using objective adherence measures were identified.ConclusionsThe Necessity-Concerns Framework is a useful conceptual model for understanding patients’ perspectives on prescribed medicines. Taking account of patients’ necessity beliefs and concerns could enhance the quality of prescribing by helping clinicians to engage patients in treatment decisions and support optimal adherence to appropriate prescriptions.

A genome-wide association scan in Crohn disease by the Wellcome Trust Case Control Consortium1 detected strong association at 6 novel loci. We tested 37 SNPs from these and other loci for association in an independent case control sample. Replication was obtained for the IRGM gene on chromosome 5q33.1 which induces autophagy (replication P = 6.6 × 10 −4 , combined P = 2.1 × 10 −10 ), and for 9 other loci including NKX2-3 and gene deserts on chromosomes 1q and 5p13. Crohn disease (CD) is a common form of chronic inflammatory bowel disease. Established CD susceptibility genes NOD2 (CARD15), IL23R and ATG16L1 2-5 showed strong evidence of association in the Wellcome Trust Case Control Consortium (WTCCC) genome-wide scan of 1748 CD cases and 2938 controls genotyped using the Affymetrix 500K chip. Six other loci also showed highly significant association. Although satisfying stringent statistical thresholds for significance (P < 5 × 10 −7 ), replication in independent panels represents a key validation step.We followed up 37 SNPs from 31 distinct loci associated at P < 10 −5 on initial analysis of the WTCCC dataset. Support for some of these markers diminished in the final WTCCC analysis after extensive data filtering1. Three other associations with genome-wide significance in the WTCCC scan produced strong evidence of replication (P≤0.01), two of which are novel. The strongest was SNP rs9292777 (P rep =2.9×10 −7 ; P comb =3.2×10 −18 ) which maps to a 1.2 Mb gene desert on chromosome 5p13.1 recently associated with CD.9 The most significant novel association was SNP rs10883365 (P rep =0.0037, P comb =3.7 × 10 −10 ), which maps within the NKX2-3 gene (NK2 transcription factor related, locus 3) on chromosome 10q24.2. Nkx2.3-deficient mice develop splenic and gut-associated lymphoid tissue abnormalities with disordered segregation of T-and B-cells.10 The second novel locus at rs9858542 (P rep =0.010, P comb =4.9×10 −8 ) on chromosome 3p21 is a 1 Mb region of high LD that contains over 20 genes, including MST1 (macrophage stimulating 1), encoding a protein which induces phagocytosis by resident peritoneal macrophages.The modest evidence of replication for SNP rs2542151 (P = 0.048) at the PTPN2 locus (protein tyrosine phosphatase, non-receptor type 2) on chromosome 18p11 (P comb = 3.2 × 10 −8 ) is of interest since PTPN2 encodes a T cell protein tyrosine phosphatase, a key negative regulator of inflammation and is also associated with Type 1 Diabetes.11 Allele frequencies for rs10761659 on chromosome 10q21, strongly associated in the WTCCC scan, were similar in replication CD cases and population controls (SOM table 2), but association in this intergenic region was recently detected in a North American whole-genome CD scan. 12Allele frequencies for most of the markers from the 25 other loci studied that did not achieve genome-wide significance in the WTCCC scan but had an initial P<10 −5 converged with control frequencies in the CD replication panel (Supplementary Table 2). Five of these loci, however, provided ev...

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53Introduction: The ESPEN guideline presents a multidisciplinary focus on clinical nutrition in