A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

Ida Surakka; John B Whitfield; Markus Perola; Peter M Visscher; Grant W Montgomery; Mario Falchi; Gonneke Willemsen; Eco J C de Geus; Patrik K E Magnusson; Kaare Christensen; Thorkild I A Sørensen; Kirsi H Pietiläinen; Taina Rantanen; Kaisa Silander; Elisabeth Widén; Juha Muilu; Iffat Rahman; Ulrika Liljedahl; Ann-Christine Syvänen; Aarno Palotie; Jaakko Kaprio; Kirsten Ohm Kyvik; Nancy L Pedersen; Dorret I Boomsma; Tim Spector; Nicholas G Martin; Samuli Ripatti; Leena Peltonen; GenomEUtwin Project

doi:10.1017/thg.2012.63

A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

Ida Surakka, John B Whitfield, Markus Perola, Peter M Visscher, Grant W Montgomery, Mario Falchi, Gonneke Willemsen, Eco J C de Geus, Patrik K E Magnusson, Kaare Christensen, Thorkild I A Sørensen, Kirsi H Pietiläinen, Taina Rantanen, Kaisa Silander, Elisabeth Widén, Juha Muilu, Iffat Rahman, Ulrika Liljedahl, Ann-Christine Syvänen, Aarno PalotieJaakko Kaprio, Kirsten Ohm Kyvik, Nancy L Pedersen, Dorret I Boomsma, Tim Spector, Nicholas G Martin, Samuli Ripatti, Leena Peltonen, GenomEUtwin Project

20 Citations (Scopus)

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).

Original language	English
Journal	Twin Research and Human Genetics
Volume	15
Issue number	6
Pages (from-to)	691-9
Number of pages	9
ISSN	1832-4274
DOIs	https://doi.org/10.1017/thg.2012.63
Publication status	Published - Dec 2012

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Surakka, I., Whitfield, J. B., Perola, M., Visscher, P. M., Montgomery, G. W., Falchi, M., Willemsen, G., de Geus, E. J. C., Magnusson, P. K. E., Christensen, K., Sørensen, T. I. A., Pietiläinen, K. H., Rantanen, T., Silander, K., Widén, E., Muilu, J., Rahman, I., Liljedahl, U., Syvänen, A-C., ... GenomEUtwin Project (2012). A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol. Twin Research and Human Genetics, 15(6), 691-9. https://doi.org/10.1017/thg.2012.63

Surakka, I, Whitfield, JB, Perola, M, Visscher, PM, Montgomery, GW, Falchi, M, Willemsen, G, de Geus, EJC, Magnusson, PKE, Christensen, K, Sørensen, TIA, Pietiläinen, KH, Rantanen, T, Silander, K, Widén, E, Muilu, J, Rahman, I, Liljedahl, U, Syvänen, A-C, Palotie, A, Kaprio, J, Kyvik, KO, Pedersen, NL, Boomsma, DI, Spector, T, Martin, NG, Ripatti, S, Peltonen, L & GenomEUtwin Project 2012, 'A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol', Twin Research and Human Genetics, vol. 15, no. 6, pp. 691-9. https://doi.org/10.1017/thg.2012.63

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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 × 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).",

author = "Ida Surakka and Whitfield, {John B} and Markus Perola and Visscher, {Peter M} and Montgomery, {Grant W} and Mario Falchi and Gonneke Willemsen and {de Geus}, {Eco J C} and Magnusson, {Patrik K E} and Kaare Christensen and S{\o}rensen, {Thorkild I A} and Pietil{\"a}inen, {Kirsi H} and Taina Rantanen and Kaisa Silander and Elisabeth Wid{\'e}n and Juha Muilu and Iffat Rahman and Ulrika Liljedahl and Ann-Christine Syv{\"a}nen and Aarno Palotie and Jaakko Kaprio and Kyvik, {Kirsten Ohm} and Pedersen, {Nancy L} and Boomsma, {Dorret I} and Tim Spector and Martin, {Nicholas G} and Samuli Ripatti and Leena Peltonen and S{\o}rensen, {Thorkild I.A.}",

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T1 - A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

AU - Surakka, Ida

AU - Whitfield, John B

AU - Perola, Markus

AU - Visscher, Peter M

AU - Montgomery, Grant W

AU - Falchi, Mario

AU - Willemsen, Gonneke

AU - de Geus, Eco J C

AU - Magnusson, Patrik K E

AU - Christensen, Kaare

AU - Sørensen, Thorkild I A

AU - Pietiläinen, Kirsi H

AU - Rantanen, Taina

AU - Silander, Kaisa

AU - Widén, Elisabeth

AU - Muilu, Juha

AU - Rahman, Iffat

AU - Liljedahl, Ulrika

AU - Syvänen, Ann-Christine

AU - Palotie, Aarno

AU - Kaprio, Jaakko

AU - Kyvik, Kirsten Ohm

AU - Pedersen, Nancy L

AU - Boomsma, Dorret I

AU - Spector, Tim

AU - Martin, Nicholas G

AU - Ripatti, Samuli

AU - Peltonen, Leena

AU - GenomEUtwin Project

PY - 2012/12

Y1 - 2012/12

N2 - 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).

AB - 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).

U2 - 10.1017/thg.2012.63

DO - 10.1017/thg.2012.63

M3 - Journal article

C2 - 23031429

SN - 1832-4274

VL - 15

SP - 691

EP - 699

JO - Twin Research

JF - Twin Research

IS - 6

ER -

A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol

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