title: A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol.
abstract: Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors(P=3.98 x 10-8). We followed up the association in further genotyped monozygotic twins (N= 1,261),which showed a moderate association for the variant (P= 0.200, same direction of an effect). In addition,we report a new association on the level of apolipoprotein A-ll (P= 4.03 x 1 o-8).
authors.affiliation: Institute for Molecular Medicine, University of Helsinki, Finland.
authors.forename: Ida
authors.initials: I
authors.lastname: Surakka
authors.forename: John B
authors.initials: JB
authors.lastname: Whitfield
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Peter M
authors.initials: PM
authors.lastname: Visscher
authors.forename: Grant W
authors.initials: GW
authors.lastname: Montgomery
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
authors.forename: Taina
authors.initials: T
authors.lastname: Rantanen
authors.forename: Kaisa
authors.initials: K
authors.lastname: Silander
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Widén
authors.forename: Juha
authors.initials: J
authors.lastname: Muilu
authors.forename: Iffat
authors.initials: I
authors.lastname: Rahman
authors.forename: Ulrika
authors.initials: U
authors.lastname: Liljedahl
authors.forename: Ann-Christine
authors.initials: AC
authors.lastname: Syvänen
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Jaakko
authors.initials: J
authors.lastname: Kaprio
authors.forename: Kirsten O
authors.initials: KO
authors.lastname: Kyvik
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Pedersen
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
authors.forename: Tim
authors.initials: T
authors.lastname: Spector
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Martin
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016633:Apolipoprotein A-II / Q000097:blood / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D007438:Introns; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D016633:Apolipoprotein A-II; D008076:Cholesterol, HDL; D020690:GTPase-Activating Proteins; C501995:SRGAP2 protein, human