New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Prevalence of and risk factors for different measures of low back pain among female nursing aides in Taiwanese nursing homes

<p>Abstract</p> <p>Background</p> <p>Although low back pain (LBP) among nursing staff, especially in nursing aides (NAs), has been a major health problem around the world, there is limited information on its prevalence in Taiwan. In addition, various measurements have been used to determine LBP; understanding the risk factors for each measurement of LBP is essential for prevention. This study aimed to assess the prevalence of and risk factors for different measures of LBP among NAs in Taiwan.</p> <p>Methods</p> <p>A cross-sectional study was conducted among 244 female NAs from 31 nursing homes in central Taiwan. A self-administered questionnaire, including the Nordic questionnaire and the Karasek's job content questionnaire, was used to collect data regarding five different measures of LBP and about demographic, physical and psychosocial factors. Also, on-site observation at the workplace was conducted to measure the frequency of five high risk patient-handling tasks.</p> <p>Results</p> <p>Based on the subjects' reports on the previous twelve months, the prevalence rates for pain lasting for at least one day, seeking of medical care, intense pain, sick leave, and chronic pain were 66.0%, 43.9%, 38.1%, 10.7%, and 8.6%, respectively. While multiple logistic regression analyses indicated that the risk factors varied with different measures of LBP, at least one high risk patient-handling task and one psychosocial factor were observed to be associated each LBP related measure. Three risk factors, including manual transfer of patients between bed/wheelchair and bath cart, perceived physical exertion, and psychological demands, were consistently associated with different measures of LBP. Besides, age was found to be associated with an increased risk of only chronic pain.</p> <p>Conclusion</p> <p>The prevalence of LBP among NAs in Taiwan is high and should be actively addressed. Certain manual patient-transfer tasks and psychological demands seemed to play more important roles in severe LBP (such as care seeking, intense pain, and sick leave) than in minor LBP (pain lasting for at least one day). Because different LBP related measures might be involved with different etiological risk factors, any LBP reduction interventions that aim to improve ergonomic and psychosocial work environments for NAs should take this information into consideration.</p

Mining the human phenome using allelic scores that index biological intermediates

J. Kaprio ja M-L. Lokki työryhmien jäseniä.It is common practice in genome-wide association studies (GWAS) to focus on the relationship between disease risk and genetic variants one marker at a time. When relevant genes are identified it is often possible to implicate biological intermediates and pathways likely to be involved in disease aetiology. However, single genetic variants typically explain small amounts of disease risk. Our idea is to construct allelic scores that explain greater proportions of the variance in biological intermediates, and subsequently use these scores to data mine GWAS. To investigate the approach's properties, we indexed three biological intermediates where the results of large GWAS meta-analyses were available: body mass index, C-reactive protein and low density lipoprotein levels. We generated allelic scores in the Avon Longitudinal Study of Parents and Children, and in publicly available data from the first Wellcome Trust Case Control Consortium. We compared the explanatory ability of allelic scores in terms of their capacity to proxy for the intermediate of interest, and the extent to which they associated with disease. We found that allelic scores derived from known variants and allelic scores derived from hundreds of thousands of genetic markers explained significant portions of the variance in biological intermediates of interest, and many of these scores showed expected correlations with disease. Genome-wide allelic scores however tended to lack specificity suggesting that they should be used with caution and perhaps only to proxy biological intermediates for which there are no known individual variants. Power calculations confirm the feasibility of extending our strategy to the analysis of tens of thousands of molecular phenotypes in large genome-wide meta-analyses. We conclude that our method represents a simple way in which potentially tens of thousands of molecular phenotypes could be screened for causal relationships with disease without having to expensively measure these variables in individual disease collections.Peer reviewe

A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

A genome-wide association search for type 2 diabetes genes in African Americans

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Integrated treatment vs. treatment-as-usual for recent onset schizophrenia; 12 year follow-up on a randomized controlled trial

Background: The aim of this study is to compare the 12-year follow-up effects on in- and outpatient services of 2 years of integrated treatment for recent-onset schizophrenia versus treatment as usual in a randomized controlled trial. Methods: 50 patients aged 18–35 years were randomized to Integrated Treatment (IT) (N = 30) or Treatment-as-Usual (TAU) (N = 20) for two years. TAU comprised optimal pharmacotherapy and outreach assertive treatment, while IT also included cognitive-behavioural family treatment, skills training, strategies for residual psychotic and non-psychotic problems and home-based crisis management. Results: There were no differences in number of days in hospital, time to readmission, number of admittances to psychiatric wards, number of involuntarily psychiatric admissions or number of outpatient contacts over a period of 12 years following the initial 2-year treatment trial. Fewer patients in the IT group were, however, involuntary admitted to hospital in the period. Conclusions: The intensive two-year psychosocial intervention seemed to have little long-term effects on use of in- and outpatient services.<p>© 2013 Sigrúnarson et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p