A recent paper in Plos Genetics, to which LifeLines contributed, assessed the interaction between serum lipid levels and body measures, especially waist-to-hip ratio. The study was coordinated by the Institute for Molecular Medicine Finland (FIMM), University of Helsinki, and Public Health Genomics Unit, National Institute for Health and Welfare, Helsinki, Finland

The investigators screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). They collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. the authors conclude that their findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus.

Source: http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1002333

 

Regularly, LifeLines reports on its progress in a detailed report.
Such reports are quarterly updated, and new information is added.

 

They contain a description of:
* The LifeLines Cohort & Biobank initiative
* Current status of participant recruitment
* Research themes
* Scientific proposals
* Scientific development
* Incidental findings and feedback to participants
* Development of LifeLines dataset
* Literature / publications.

Here you can find the latest LifeLines report.

A recent paper in the New England Journal of Medicine discussed the results of a genomewide association study in subjects with Dupuytren's disease. Genomewide data of participants of the LifeLines Cohort Study served as controls.

Dupuytren's disease is a benign fibromatosis of the hands and fingers that leads to flexion contractures. We hypothesized that multiple genetic and environmental factors influence susceptibility to this disease and sought to identify susceptibility genes to better understand its pathogenesis.

A genomewide association study was performed in 960 Dutch persons with Dupuytren's disease and 3117 LifeLines controls (the discovery set) to test for association between the disease and genetic markers. The 35 single-nucleotide polymorphisms (SNPs) which were most strongly associated with Dupuytren's disease were subsequently tested in three additional, independent case series comprising a total of 1365 affected persons and 8445 controls from Germany, the United Kingdom, and The Netherlands.

Initially, a significant genomewide association was observed between Dupuytren's disease and 8 SNPs at three loci. Tests of replication and joint analysis of all data from 2325 patients with Dupuytren's disease and 11,562 controls yielded an association with 11 SNPs from nine different loci. Six of these loci contain genes known to be involved in the Wnt-signaling pathway: WNT4 (rs7524102), SFRP4 (rs16879765), WNT2 (rs4730775), RSPO2 (rs611744), SULF1 (rs2912522), and WNT7B (rs6519955).

This is the largest study until now in Dupuytren's disease, and it implicates nine different loci involved in genetic susceptibility to this disease. The authors conclude that aberrations in the Wnt-signaling pathway are key to the process of fibromatosis in Dupuytren's disease.

Source: http://www.nejm.org/doi/full/10.1056/NEJMoa1101029

^{Picture from: Howard J, et al, BMC Musculoskeletal Disorders, Vol.4, Issue  1}

 

In a recently published paper in Nature Genetics, a large consortium of researchers have reported six new loci which influence pulse pressure and mean arterial pressure. Investigators from the LifeLines study, amongst others prof. Stolk, prof. Snieder, and dr. van der Klauw, participated in this paper. In discovery (n=74,064) and follow-up studies (n=48,607), the researchers identified four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians.

For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits.

The authors conclude that these findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP.

The full paper can be found on the Nature Genetics website: http://www.nature.com/ng/journal/v43/n10/full/ng.922.html

 

In the following paper the background of LifeLines is explained in detail.
Title: Universal risk factors for multifactorial diseases: LifeLines: a three-generation population-based study.
Authors: Stolk RP, Rosmalen JG, Postma DS, de Boer RA, Navis G, Slaets JP, Ormel J, Wolffenbuttel BHR.
Journal: Eur J Epidemiol 2008;23(1):67-74.

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