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A Genome-Wide Association Study of Monozygotic Twin-Pairs Suggests a Locus Related to Variability of Serum High-Density Lipoprotein Cholesterol

  • Ida Surakka (a1) (a2), John B. Whitfield (a3), Markus Perola (a1) (a2) (a4), Peter M. Visscher (a5), Grant W. Montgomery (a3), Mario Falchi (a6), Gonneke Willemsen (a7), Eco J. C. de Geus (a7), Patrik K. E. Magnusson (a8), Kaare Christensen (a9) (a10), Thorkild I. A. Sørensen (a11) (a12), Kirsi H. Pietiläinen (a1) (a13), Taina Rantanen (a14), Kaisa Silander (a1), Elisabeth Widén (a1), Juha Muilu (a1), Iffat Rahman (a8), Ulrika Liljedahl (a15), Ann-Christine Syvänen (a15), Aarno Palotie (a1) (a16) (a17) (a18), Jaakko Kaprio (a1) (a19) (a20), Kirsten O. Kyvik (a21) (a22), Nancy L. Pedersen (a8), Dorret I. Boomsma (a7), Tim Spector (a23), Nicholas G. Martin (a3), Samuli Ripatti (a1) (a2) (a16) and Leena Peltonen...
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 × 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-II (P = 4.03 × 10−8).

Copyright
Corresponding author
address for correspondence: Samuli Ripatti, Institute for Molecular Medicine, Finland, FIMM, PO Box 20, University of Helsinki, Finland. E-mail: samuli.ripatti@fimm.fi
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Twin Research and Human Genetics
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