Genome-wide association analysis of metabolic traits in a birth cohort from a founder population

Nelson Freimer and colleagues report the first genome-wide association study of a longitudinal birth cohort (the Northern Finland Birth Cohort 1966). The results include new associations for nine quantitative metabolic traits. Genome-wide association studies (GWAS) of longitudinal birth cohorts enab...

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Veröffentlicht in:	Nature genetics Jg. 41; H. 1; S. 35 - 46
Hauptverfasser:	Sabatti, Chiara, Service, Susan K, Hartikainen, Anna-Liisa, Pouta, Anneli, Ripatti, Samuli, Brodsky, Jae, Jones, Chris G, Zaitlen, Noah A, Varilo, Teppo, Kaakinen, Marika, Sovio, Ulla, Ruokonen, Aimo, Laitinen, Jaana, Jakkula, Eveliina, Coin, Lachlan, Hoggart, Clive, Collins, Andrew, Turunen, Hannu, Gabriel, Stacey, Elliot, Paul, McCarthy, Mark I, Daly, Mark J, Järvelin, Marjo-Riitta, Freimer, Nelson B, Peltonen, Leena
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	New York Nature Publishing Group US 01.01.2009 Nature Publishing Group
Schlagworte:	Adult Agriculture Alcohol use Animal Genetics and Genomics Biological and medical sciences Biomedical and Life Sciences Biomedicine Blood Pressure Body Mass Index Cancer Research Cardiovascular diseases Cohort Studies Delta-5 Fatty Acid Desaturase Diabetes Disease Environmental health Finland Founder Effect Fundamental and applied biological sciences. Psychology Gene Function Gene mapping Genetic aspects Genetics Genetics of eukaryotes. Biological and molecular evolution Genome-Wide Association Study Genotype Genotype & phenotype Genotype-environment interactions Geography Human Genetics Humans Insulin Linguistics Metabolic Networks and Pathways - genetics Metabolic syndrome Parturition - genetics Phenotype Polymorphism, Single Nucleotide - genetics Population Dynamics Population Groups - genetics Quantitative Trait Loci - genetics Quantitative Trait, Heritable Reproducibility of Results Risk factors Single nucleotide polymorphisms Type 2 diabetes Variables Womens health Finland United States Birth Association
ISSN:	1061-4036, 1546-1718, 1546-1718
Online-Zugang:	Volltext
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Zusammenfassung:	Nelson Freimer and colleagues report the first genome-wide association study of a longitudinal birth cohort (the Northern Finland Birth Cohort 1966). The results include new associations for nine quantitative metabolic traits. Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 ( LXRA ), low-density lipoprotein with AR and FADS1 - FADS2 , glucose with MTNR1B , and insulin with PANK1 . Two of these new associations emerged after adjustment of results for body mass index. Gene–environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 The study was designed by L.P., N.B.F., C.S., M.I.M., M.J.D., P.E., M.-R.J. and S.K.S. Information on traits was collected and maintained by M.-R.J., A.-L.H., A.P., A.R. and J.L. Genotyping was supervised by S.G. Database support was provided by H.T., U.S. and M.K. Statistical analysis was performed by C.S., S.K.S., A.C., C.G.J., J.B., N.A.Z., and M.J.D. S.R., E.J. and T.V. contributed to the analysis of the Finnish genetic signature. L.C., C.H. and P.E. participated in discussion of results. The manuscript was written by C.S., S.K.S., N.B.F. and L.P. All authors reviewed the manuscript. AUTHOR CONTRIBUTIONS These authors contributed equally to this work.
ISSN:	1061-4036 1546-1718 1546-1718
DOI:	10.1038/ng.271