Additional file 1: of Genetic risk score and risk of stage 3 chronic kidney disease

Characteristics of SNPs included in the genetic risk score. The supplemental table provides characteristics of the 53 SNPs included in the genetic risk score. (DOC 79 kb

Multi-criteria assessment approach for a residential building retrofit in Norway

This paper presents a multi-criteria assessment approach for a wide range of energy efficient measures and their combinations applied for a residential building retrofit in Norway. A number of passive, active and renewable energy efficient measures (EEMs) have been selected and defined. Based on the level of energy saving potentials, these EEMs have been combined into 18 retrofit combination packages (COMBs) and grouped into various retrofit levels (Moderate Retrofit-I, II, III and Extensive Retrofit). The annual primary energy consumptions (heating, hot water and electricity) for the proposed combination packages were simulated in IESVE building energy simulation software. This is then followed by two levels of assessments: i) the comprehensive assessments of the key retrofit priorities including primary energy reduction, global costs, payback period and the carbon emission reduction and ii) social assessment with the aim to represent various stakeholders’ views on the selected COMBs using a metric of weighting factors. Based on this, a multi-criteria assessment approach featuring a novel ranking factor (EEES) taking into account of energy, economic, environmental and social aspects during retrofit process was adopted. This approach quantifies different stakeholders’ perspectives on the proposed COMBs, which could enable various stakeholders’ involvement in the retrofit decision making process. It was concluded that COMB 05 and 06, which include only 2–3 passive and active EEMs have been ranked and chosen as the most favourable retrofit solutions, with EEES value equalled to 25.6 from various stakeholders’ perspectives. The impacts of changing renewable energy prices and PV generated feed-in tariff rates on the global costs, carbon reductions and primary energy consumptions of the proposed COMBs, which have rarely been analysed in literature, are numerically investigated in this research. Such renewable EEMs which are greatly recommended by the European Commission, are expected to gain further support from national level government renewable incentives. Therefore, it is envisaged that in the long term, Extensive Retrofits incorporating mostly renewable EEMs could become more affordable and cost effective.</div

Schema of instrumental variable analyses conducted in order to infer the potential causal relations between DNA methylation, gene expression, BMI, and adiposity-related disease.

<p>Schema of instrumental variable analyses conducted in order to infer the potential causal relations between DNA methylation, gene expression, BMI, and adiposity-related disease.</p

Fifty novel replicated differentially methylated CpGs associated with BMI sorted by <i>p-</i>value in the discovery cohorts.

<p>Fifty novel replicated differentially methylated CpGs associated with BMI sorted by <i>p-</i>value in the discovery cohorts.</p

Annotated genes of replicated differentially methylated CpGs identified in the BMI epigenome-wide association study.

<p>Genes are grouped by association with gene expression, association of gene expression with BMI, and Mendelian randomization analyses for causal support. Duplicate gene names within the same group are not shown. Figure does not include 18 intergenic CpGs without a gene annotation. BMI, body mass index; EWAS, epigenome-wide association study.</p

Study characteristics of the Framingham Heart Study and Lothian Birth Cohort participants (discovery cohorts) at the time of DNA methylation assays.

<p>Study characteristics of the Framingham Heart Study and Lothian Birth Cohort participants (discovery cohorts) at the time of DNA methylation assays.</p

Series of analyses conducted for the epigenome-wide association study of body mass index.

<p>ARIC, Atherosclerosis Risk in Communities; BMI, body mass index; DHS, DNase I hypersensitive site; FHS, Framingham Heart Study; GO, Gene Ontology; GOLDN, Genetics of Lipid Lowering Drugs and Diet Network; GWAS, genome-wide association study; LBC, Lothian Birth Cohorts; MR, Mendelian randomization; PIVUS, Prospective Investigation of the Vasculature in Uppsala Seniors; TSS, transcription start site.</p

Association results from 11 replicated CpGs with significant three-way associations in whole blood between CpG methylation and BMI, CpG methylation and gene expression, and gene expression and BMI.

<p>Association results from 11 replicated CpGs with significant three-way associations in whole blood between CpG methylation and BMI, CpG methylation and gene expression, and gene expression and BMI.</p

Change in albuminuria and subsequent risk of end-stage kidney disease: an individual participant-level consortium meta-analysis of observational studies

Background: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. Methods: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. Findings: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0·83 (95% CI 0·74–0·94), decreasing to 0·78 (0·66–0·92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction<0·0001). In individuals with baseline ACR of 300 mg/g or higher, a 30% decrease in ACR over 2 years was estimated to confer a more than 1% absolute reduction in 10-year risk of end-stage kidney disease, even at early stages of chronic kidney disease. Results were generally similar when we used change in PCR and when study populations from clinical trials were assessed. Interpretation: Change in albuminuria was consistently associated with subsequent risk of end-stage kidney disease across a range of cohorts, lending support to the use of change in albuminuria as a surrogate endpoint for end-stage kidney disease in clinical trials of progression of chronic kidney disease in the setting of increased albuminuria

Adiposity and risk of decline in glomerular filtration rate: meta-analysis of individual participant data in a global consortium

OBJECTIVE:To evaluate the associations between adiposity measures (body mass index, waist circumference, and waist-to-height ratio) with decline in glomerular filtration rate (GFR) and with all cause mortality. DESIGN:Individual participant data meta-analysis. SETTING:Cohorts from 40 countries with data collected between 1970 and 2017. PARTICIPANTS:Adults in 39 general population cohorts (n=5 459 014), of which 21 (n=594 496) had data on waist circumference; six cohorts with high cardiovascular risk (n=84 417); and 18 cohorts with chronic kidney disease (n=91 607). MAIN OUTCOME MEASURES:GFR decline (estimated GFR decline ≥40%, initiation of kidney replacement therapy or estimated GFR <10 mL/min/1.73 m2) and all cause mortality. RESULTS:Over a mean follow-up of eight years, 246 607 (5.6%) individuals in the general population cohorts had GFR decline (18 118 (0.4%) end stage kidney disease events) and 782 329 (14.7%) died. Adjusting for age, sex, race, and current smoking, the hazard ratios for GFR decline comparing body mass indices 30, 35, and 40 with body mass index 25 were 1.18 (95% confidence interval 1.09 to 1.27), 1.69 (1.51 to 1.89), and 2.02 (1.80 to 2.27), respectively. Results were similar in all subgroups of estimated GFR. Associations weakened after adjustment for additional comorbidities, with respective hazard ratios of 1.03 (0.95 to 1.11), 1.28 (1.14 to 1.44), and 1.46 (1.28 to 1.67). The association between body mass index and death was J shaped, with the lowest risk at body mass index of 25. In the cohorts with high cardiovascular risk and chronic kidney disease (mean follow-up of six and four years, respectively), risk associations between higher body mass index and GFR decline were weaker than in the general population, and the association between body mass index and death was also J shaped, with the lowest risk between body mass index 25 and 30. In all cohort types, associations between higher waist circumference and higher waist-to-height ratio with GFR decline were similar to that of body mass index; however, increased risk of death was not associated with lower waist circumference or waist-to-height ratio, as was seen with body mass index. CONCLUSIONS:Elevated body mass index, waist circumference, and waist-to-height ratio are independent risk factors for GFR decline and death in individuals who have normal or reduced levels of estimated GFR