title: Increasing insulin resistance accentuates the effect of triglyceride-associated loci on serum triglycerides during 5 years.
abstract: Blood concentrations of triglycerides are influenced by genetic factors as well as a number of environmental factors, including adiposity and glucose homeostasis. The aim was to investigate the association between a serum triglyceride weighted genetic risk score (wGRS) and changes in fasting serum triglyceride level over 5 years and to test whether the effect of the wGRS was modified by 5 year changes of adiposity, insulin resistance, and lifestyle factors. A total of 3,474 nondiabetic individuals from the Danish Inter99 cohort participated in both the baseline and 5 year follow-up physical examinations and had information on the wGRS comprising 39 genetic variants. In a linear regression model adjusted for age, sex, and baseline serum triglyceride, the wGRS was associated with increased serum triglyceride levels over 5 years [per allele effect = 1.3% (1.0-1.6%); P = 1.0 × 10-17]. This triglyceride-increasing effect of the wGRS interacted with changes in insulin resistance (Pinteraction= 1.5 × 10-6). This interaction indicated that the effect of the wGRS was stronger in individuals who became more insulin resistant over 5 years. In conclusion, our findings suggest that increased genetic risk load is associated with a larger increase in fasting serum triglyceride levels in nondiabetic individuals during 5 years of follow-up. This effect of the wGRS is accentuated by increasing insulin resistance.
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Johanne M
authors: JM
authors: Justesen
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: ehm.andersson@sund.ku.dk.
authors: Ehm A
authors: EA
authors: Andersson
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Kristine H
authors: KH
authors: Allin
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Camilla H
authors: CH
authors: Sandholt
authors: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Medicine, University of Aalborg, Aalborg, Denmark.
authors: Torben
authors: T
authors: Jørgensen
authors: Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark; Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
authors: Allan
authors: A
authors: Linneberg
authors: Steno Diabetes Center, Gentofte, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors: Marit E
authors: ME
authors: Jørgensen
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
authors: Torben
authors: T
authors: Hansen
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Oluf
authors: O
authors: Pedersen
authors: The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors: Niels
authors: N
authors: Grarup
mesh_terms: D050154:Adiposity; D000328:Adult; D050171:Dyslipidemias / Q000097:blood / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*
chemical_list: D014280:Triglycerides
keywords: genetic association; genetic risk score; interaction