Kristiansson K.,Public Health Genomics Unit |
Kristiansson K.,Institute for Molecular Medicine Finland FIMM |
Kristiansson K.,University of Helsinki |
Perola M.,Public Health Genomics Unit |
And 50 more authors.
Circulation: Cardiovascular Genetics | Year: 2012
Background-Genome-wide association (GWA) studies have identified several susceptibility loci for metabolic syndrome (MetS) component traits, but have had variable success in identifying susceptibility loci to the syndrome as an entity. We conducted a GWA study on MetS and its component traits in 4 Finnish cohorts consisting of 2637 MetS cases and 7927 controls, both free of diabetes, and followed the top loci in an independent sample with transcriptome and nuclear magnetic resonance-based metabonomics data. Furthermore, we tested for loci associated with multiple MetS component traits using factor analysis, and built a genetic risk score for MetS. Methods and Results-A previously known lipid locus, APOA1/C3/A4/A5 gene cluster region (SNP rs964184), was associated with MetS in all 4 study samples (P=7.23×10-9 in meta-analysis). The association was further supported by serum metabolite analysis, where rs964184 was associated with various very low density lipoprotein, triglyceride, and high-density lipoprotein metabolites (P=0.024 -1.88×10-5). Twenty-two previously identified susceptibility loci for individual MetS component traits were replicated in our GWA and factor analysis. Most of these were associated with lipid phenotypes, and none with 2 or more uncorrelated MetS components. A genetic risk score, calculated as the number of risk alleles in loci associated with individual MetS traits, was strongly associated with MetS status. Conclusions-Our findings suggest that genes from lipid metabolism pathways have the key role in the genetic background of MetS. We found little evidence for pleiotropy linking dyslipidemia and obesity to the other MetS component traits, such as hypertension and glucose intolerance. © 2012 American Heart Association, Inc.
Von Bondorff M.B.,University of Jyväskylä |
Tormakangas T.,University of Jyväskylä |
Salonen M.,Diabetes Prevention Unit |
Salonen M.,Folkhalsan Research Center |
And 9 more authors.
PLoS ONE | Year: 2015
Background There is some evidence linking sub-optimal prenatal development to an increased risk of disability pension (DP). Our aim was to investigate whether body size at birth was associated with transitioning into all-cause and cause-specific DP during the adult work career. Methods 10 682 people born in 1934-44 belonging to the Helsinki Birth Cohort Study had data on birth weight extracted from birth records, and on time, type and reason of retirement between1971 and 2011 extracted from the Finnish Centre for Pensions. Results Altogether 21.3% transitioned into DP during the 40-year follow-up, mainly due to mental disorders, musculoskeletal disorders and cardiovascular disease. Average age of transitioning into DP was 51.3 (SD 8.4) for men and 52.2 (SD 7.6) for women. Cohort members who did not transition into DP retired 10 years later on average. Among men, higher birth weight was associated with a lower hazard of transitioning into DP, adjusted hazard ratio (HR) being 0.94 (95% confidence interval [CI] 0.88-0.99 for 1 SD increase in birth weight). For DP due to mental disorders the adjusted HR was 0.90, 95% CI 0.81, 0.99. A similar but non-significant trend was found for DP due to cardiovascular disease. Among women there were no associations between body size at birth and all-cause DP (p for interaction gender birth weight on DP p = 0.007). Conclusions Among men disability pension, particularly due to mental disorders, may have its origins in prenatal development. Given that those who retire due to mental health problems are relatively young, the loss to the workforce is substantial. © 2015 von Bondorff et al.