title: Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
abstract: 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.
authors.affiliation: Department of Human Genetics and Los Angeles, Los Angeles, California 90095, USA.
authors.forename: Chiara
authors.initials: C
authors.lastname: Sabatti
authors.forename: Susan K
authors.initials: SK
authors.lastname: Service
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Jae
authors.initials: J
authors.lastname: Brodsky
authors.forename: Chris G
authors.initials: CG
authors.lastname: Jones
authors.forename: Noah A
authors.initials: NA
authors.lastname: Zaitlen
authors.forename: Teppo
authors.initials: T
authors.lastname: Varilo
authors.forename: Marika
authors.initials: M
authors.lastname: Kaakinen
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Jaana
authors.initials: J
authors.lastname: Laitinen
authors.forename: Eveliina
authors.initials: E
authors.lastname: Jakkula
authors.forename: Lachlan
authors.initials: L
authors.lastname: Coin
authors.forename: Clive
authors.initials: C
authors.lastname: Hoggart
authors.forename: Andrew
authors.initials: A
authors.lastname: Collins
authors.forename: Hannu
authors.initials: H
authors.lastname: Turunen
authors.forename: Stacey
authors.initials: S
authors.lastname: Gabriel
authors.forename: Paul
authors.initials: P
authors.lastname: Elliot
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Daly
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Nelson B
authors.initials: NB
authors.lastname: Freimer
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000328:Adult; D001794:Blood Pressure; D015992:Body Mass Index; D015331:Cohort Studies; D000090943:Delta-5 Fatty Acid Desaturase; D005387:Finland; D018703:Founder Effect; D055106:Genome-Wide Association Study; D005838:Genotype; D005843:Geography; D006801:Humans; D008037:Linguistics; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D036801:Parturition / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011157:Population Dynamics; D044382:Population Groups / Q000235:genetics*; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable; D015203:Reproducibility of Results