Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
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.
Sabatti
Chiara
C
Department of Human Genetics and Los Angeles, Los Angeles, California 90095, USA.
Service
Susan K
SK
Hartikainen
Anna-Liisa
AL
Pouta
Anneli
A
Ripatti
Samuli
S
Brodsky
Jae
J
Jones
Chris G
CG
Zaitlen
Noah A
NA
Varilo
Teppo
T
Kaakinen
Marika
M
Sovio
Ulla
U
Ruokonen
Aimo
A
Laitinen
Jaana
J
Jakkula
Eveliina
E
Coin
Lachlan
L
Hoggart
Clive
C
Collins
Andrew
A
Turunen
Hannu
H
Gabriel
Stacey
S
Elliot
Paul
P
McCarthy
Mark I
MI
Daly
Mark J
MJ
Järvelin
Marjo-Riitta
MR
Freimer
Nelson B
NB
Peltonen
Leena
L
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