Comparison of participant information and informed consent forms of five European studies in genetic isolated populations

Mascalzoni, Deborah; Janssens, A. Cecile J.W.; Stewart, Alison; Pramstaller, Peter P.; Gyllensten, Ulf; Rudan, Igor; Duijn, Cornelia M. van; Wilson, James F.; Campbell, Harry; Quillan, Ruth M. C.

doi:10.1038/ejhg.2009.155

Cited by 31 publications

(31 citation statements)

References 38 publications

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“…In case the participant was not full age, a legal guardian signed additionally. The procedure which was used to obtain informed consent and the respective informed consent form has been recently discussed in the light of present ethical guidelines [17]. Since we are working with a study cohort from a limited area, deposition of the raw data might allow for person identification.…”

Section: Methodsmentioning

confidence: 99%

Continuous Aging of the Human DNA Methylome Throughout the Human Lifespan

2013

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DNA methylation plays an important role in development of disease and the process of aging. In this study we examine DNA methylation at 476,366 sites throughout the genome of white blood cells from a population cohort (N = 421) ranging in age from 14 to 94 years old. Age affects DNA methylation at almost one third (29%) of the sites (Bonferroni adjusted P-value <0.05), of which 60.5% becomes hypomethylated and 39.5% hypermethylated with increasing age. DNA methylation sites that are located within CpG islands (CGIs) more often become hypermethylated compared to sites outside an island. CpG sites in promoters are more unaffected by age, whereas sites in enhancers more often becomes hypo- or hypermethylated. Hypermethylated sites are overrepresented among genes that are involved in DNA binding, transcription regulation, processes of anatomical structure and developmental process and cortex neuron differentiation (P-value down to P = 9.14*10−67). By contrast, hypomethylated sites are not strongly overrepresented among any biological function or process. Our results indicate that the 23% of the variation in DNA methylation is attributed chronological age, and that hypermethylation is more site-specific than hypomethylation. It appears that the change in DNA methylation partly overlap with regions that change histone modifications with age, indicating an interaction between the two major epigenetic mechanisms. Epigenetic modifications and change in gene expression over time most likely reflects the natural process of aging and variation between individuals might contribute to the development of age-related phenotypes and diseases such as type II diabetes, autoimmune and cardiovascular disease.

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Section: Methodsmentioning

confidence: 99%

Continuous Aging of the Human DNA Methylome Throughout the Human Lifespan

2013

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“…In cases where the participant was not of age, a legal guardian signed additionally. The procedure that was used to obtain informed consent and the respective informed consent form have recently been discussed in light of present ethical guidelines (27).…”

Section: Methodsmentioning

confidence: 99%

Identification of genetic variants influencing the human plasma proteome

Johansson

Enroth

Palmblad

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Genetic variants influencing the transcriptome have been extensively studied. However, the impact of the genetic factors on the human proteome is largely unexplored, mainly due to lack of suitable high-throughput methods. Here we present unique and comprehensive identification of genetic variants affecting the human plasma protein profile by combining high-throughput and highresolution mass spectrometry (MS) with genome-wide SNP data. We identified and quantified the abundance of 1,056 trypticdigested peptides, representing 163 proteins in the plasma of 1,060 individuals from two population-based cohorts. The abundance level of almost one-fifth (19%) of the peptides was found to be heritable, with heritability ranging from 0.08 to 0.43. The levels of 60 peptides from 25 proteins, 15% of the proteins studied, were influenced by cis-acting SNPs. We identified and replicated individual cis-acting SNPs (combined P value ranging from 3.1 × 10 −52 to 2.9 × 10 −12 ) influencing 11 peptides from 5 individual proteins. These SNPs represent both regulatory SNPs and nonsynonymous changes defining well-studied disease alleles such as the e4 allele of apolipoprotein E (APOE), which has been shown to increase risk of Alzheimer's disease. Our results show that high-throughput mass spectrometry represents a promising method for large-scale characterization of the human proteome, allowing for both quantification and sequencing of individual proteins. Abundance and peptide composition of a protein plays an important role in the etiology, diagnosis, and treatment of a number of diseases. A better understanding of the genetic impact on the plasma proteome is therefore important for evaluating potential biomarkers and therapeutic agents for common diseases.protein quantitative trait loci | population proteomics O ur understanding of the impact of genetic variation on human traits has been greatly advanced using high-throughput SNP genotyping and massively parallel sequencing. The large number of genome-wide association studies (GWAS) performed have resulted in the identification of hundreds of SNPs that are associated with human traits and diseases (1, 2). The functional impact of most of the SNPs influencing human traits has not been well characterized. Whereas nonsynonymous SNPs affect the amino acid sequence directly and could alter the function of the resulting protein, other SNPs may have an impact on splice sites (3) or influence amount or stability of the mRNA (4). GWAS studies relating the genetic variability to the transcript profile have identified a number of cis-regulatory SNPs affecting expression quantitative traits (eQTs) (5, 6). Evidently, the expression of many genes is influenced by a nearby SNP, with cis-regulatory SNPs being overrepresented among SNPs associated with human phenotypes (1). Studies have also addressed the impact of genetic variability on levels of endogenous metabolites, such as sugars, biogenic amines, acylcarnitines, and glycerophospho-and sphingolipids, which can be measured in either human urin...

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“…In case the participant was not full age, a legal guardian also signed. The procedure, which was used to obtain informed consent and the respective informed consent form, has been recently discussed in the light of present ethical guidelines (30). …”

Section: Methodsmentioning

confidence: 99%

Prevalence and sensitization of atopic allergy and coeliac disease in the Northern Sweden Population Health Study

Enroth

Dahlbom

Hansson

et al. 2013

International Journal of Circumpolar Health

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BackgroundAtopic allergy is effected by a number of environmental exposures, such as dry air and time spent outdoors, but there are few estimates of the prevalence in populations from sub-arctic areas.ObjectiveTo determine the prevalence and severity of symptoms of food, inhalation and skin-related allergens and coeliac disease (CD) in the sub-arctic region of Sweden. To study the correlation between self-reported allergy and allergy test results. To estimate the heritability of these estimates.Study designThe study was conducted in Karesuando and Soppero in Northern Sweden as part of the Northern Sweden Population Health Study (n=1,068). We used a questionnaire for self-reported allergy and CD status and measured inhalation-related allergens using Phadiatop, food-related allergens using the F×5 assay and IgA and IgG antibodies against tissue transglutaminase (anti-tTG) to indicate prevalence of CD.ResultsThe prevalence of self-reported allergy was very high, with 42.3% reporting mild to severe allergy. Inhalation-related allergy was reported in 26.7%, food-related allergy in 24.9% and skin-related allergy in 2.4% of the participants. Of inhalation-related allergy, 11.0% reported reactions against fur and 14.6% against pollen/grass. Among food-related reactions, 14.9% reported milk (protein and lactose) as the cause. The IgE measurements showed that 18.4% had elevated values for inhalation allergens and 11.7% for food allergens. Self-reported allergies and symptoms were positively correlated (p<0.01) with age- and sex-corrected inhalation allergens. Allergy prevalence was inversely correlated with age and number of hours spent outdoors. High levels of IgA and IgG anti-tTG antibodies, CD-related allergens, were found in 1.4 and 0.6% of participants, respectively. All allergens were found to be significantly (p<3 e–10) heritable, with estimated heritabilities ranging from 0.34 (F×5) to 0.65 (IgA).ConclusionsSelf-reported allergy correlated well with the antibody measurements. The prevalence of allergy was highest in the young and those working inside. Heritability of atopy and sensitization was high. The prevalence of CD-related autoantibodies was high and did not coincide with the self-reported allergy.

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Comparison of participant information and informed consent forms of five European studies in genetic isolated populations

Cited by 31 publications

References 38 publications

Continuous Aging of the Human DNA Methylome Throughout the Human Lifespan

Continuous Aging of the Human DNA Methylome Throughout the Human Lifespan

Identification of genetic variants influencing the human plasma proteome

Prevalence and sensitization of atopic allergy and coeliac disease in the Northern Sweden Population Health Study

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