Genetic association analysis of LARS2 with type 2 diabetes

被引：7

作者：

Reiling, E. ^{[1
]}

Jafar-Mohammadi, B. ^{[28
,29
]}

van't Riet, E. ^{[2
,3
]}

Weedon, M. N. ^{[4
,5
]}

van Vliet-Ostaptchouk, J. V. ^{[6
,27
]}

Hansen, T. ^{[7
,22
,26
]}

Saxena, R. ^{[8
,25
]}

van Haeften, T. W. ^{[10
]}

Arp, P. A. ^{[11
]}

Das, S. ^{[29
]}

Nijpels, G. ^{[2
,12
]}

Groenewoud, M. J. ^{[1
]}

van Hove, E. C. ^{[1
]}

Uitterlinden, A. G. ^{[11
]}

Smit, J. W. A. ^{[13
]}

Morris, A. D. ^{[21
]}

Doney, A. S. F. ^{[21
]}

Palmer, C. N. A. ^{[21
]}

Guiducci, C. ^{[8
,25
]}

Hattersley, A. T. ^{[4
,5
]}

Frayling, T. M. ^{[4
,5
]}

Pedersen, O. ^{[7
,14
,15
,26
]}

Slagboom, P. E. ^{[9
]}

Altshuler, D. M. ^{[8
,16
,17
,24
,25
]}

Groop, L. ^{[18
,19
]}

Romijn, J. A. ^{[13
]}

Maassen, J. A. ^{[1
,20
]}

Hofker, M. H. ^{[6
,27
]}

Dekker, J. M. ^{[2
,3
]}

McCarthy, M. I. ^{[23
,28
,29
]}

't Hart, L. M. ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, Dept Mol Cell Biol, NL-2300 RC Leiden, Netherlands

[2] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands

[3] Vrije Univ Amsterdam Med Ctr, Dept Epidemiol & Biostat, Amsterdam, Netherlands

[4] Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England

[5] Peninsula Med Sch, Diabet Genet Inst Biomed & Clin Sci, Exeter, Devon, England

[6] Univ Med Ctr Groningen, Dept Pathol & Med Biol, Med Biol Sect, NL-9713 AV Groningen, Netherlands

[7] Steno Diabet Ctr, DK-2820 Gentofte, Denmark

[8] MIT, Program Med & Populat Genet, Broad Inst, Cambridge, MA 02139 USA

[9] Leiden Univ, Med Ctr, Dept Med Stat, NL-2300 RC Leiden, Netherlands

[10] Univ Med Ctr Utrecht, Dept Internal Med, Utrecht, Netherlands

[11] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands

[12] Vrije Univ Amsterdam Med Ctr, Dept Gen Practice, Amsterdam, Netherlands

[13] Leiden Univ, Med Ctr, Dept Endocrinol, NL-2300 RC Leiden, Netherlands

[14] Aarhus Univ, Fac Hlth Sci, Aarhus, Denmark

[15] Univ Copenhagen, Fac Hlth Sci, Copenhagen, Denmark

[16] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[17] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA

[18] Lund Univ, Clin Res Ctr, Dept Clin Sci, Malmo Univ Hosp, Malmo, Sweden

[19] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland

[20] Vrije Univ Amsterdam Med Ctr, Dept Endocrinol, Amsterdam, Netherlands

[21] Univ Dundee, Ninewells Hosp & Med Sch, Diabet Res Grp, Dundee DD1 9SY, Scotland

[22] Univ So Denmark, Fac Hlth Sci, Odense, Denmark

[23] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[24] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA

[25] Harvard Univ, Cambridge, MA 02138 USA

[26] Hagedorn Res Inst, Gentofte, Denmark

[27] Univ Groningen, Groningen, Netherlands

[28] Univ Oxford, Oxford Biomed Res Ctr, Natl Inst Hlth Res, Oxford, England

[29] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England

来源：

DIABETOLOGIA | 2010年 / 53卷 / 01期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

Genetics; LARS2; Mitochondria; SNP; Type; 2; diabetes; GENOME-WIDE ASSOCIATION; MELLITUS; GLUCOSE; REPLICATION; LOCI; DETERMINANTS; DYSFUNCTION; POPULATION; PREVALENCE; SELECTION;

D O I：

10.1007/s00125-009-1557-7

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

LARS2 has been previously identified as a potential type 2 diabetes susceptibility gene through the low-frequency H324Q (rs71645922) variant (minor allele frequency [MAF] 3.0%). However, this association did not achieve genome-wide levels of significance. The aim of this study was to establish the true contribution of this variant and common variants in LARS2 (MAF > 5%) to type 2 diabetes risk. We combined genome-wide association data (n = 10,128) from the DIAGRAM consortium with independent data derived from a tagging single nucleotide polymorphism (SNP) approach in Dutch individuals (n = 999) and took forward two SNPs of interest to replication in up to 11,163 Dutch participants (rs17637703 and rs952621). In addition, because inspection of genome-wide association study data identified a cluster of low-frequency variants with evidence of type 2 diabetes association, we attempted replication of rs9825041 (a proxy for this group) and the previously identified H324Q variant in up to 35,715 participants of European descent. No association between the common SNPs in LARS2 and type 2 diabetes was found. Our replication studies for the two low-frequency variants, rs9825041 and H324Q, failed to confirm an association with type 2 diabetes in Dutch, Scandinavian and UK samples (OR 1.03 [95% CI 0.95-1.12], p = 0.45, n = 31,962 and OR 0.99 [0.90-1.08], p = 0.78, n = 35,715 respectively). In this study, the largest study examining the role of sequence variants in LARS2 in type 2 diabetes susceptibility, we found no evidence to support previous data indicating a role in type 2 diabetes susceptibility.

引用

页码：103 / 110

页数：8

共 26 条

[1] A haplotype map of the human genome [J].

Altshuler, D ;

Brooks, LD ;

Chakravarti, A ;

Collins, FS ;

Daly, MJ ;

Donnelly, P ;

Gibbs, RA ;

Belmont, JW ;

Boudreau, A ;

Leal, SM ;

Hardenbol, P ;

Pasternak, S ;

Wheeler, DA ;

Willis, TD ;

Yu, FL ;

Yang, HM ;

Zeng, CQ ;

Gao, Y ;

Hu, HR ;

Hu, WT ;

Li, CH ;

Lin, W ;

Liu, SQ ;

Pan, H ;

Tang, XL ;

Wang, J ;

Wang, W ;

Yu, J ;

Zhang, B ;

Zhang, QR ;

Zhao, HB ;

Zhao, H ;

Zhou, J ;

Gabriel, SB ;

Barry, R ;

Blumenstiel, B ;

Camargo, A ;

Defelice, M ;

Faggart, M ;

Goyette, M ;

Gupta, S ;

Moore, J ;

Nguyen, H ;

Onofrio, RC ;

Parkin, M ;

Roy, J ;

Stahl, E ;

Winchester, E ;

Ziaugra, L ;

Shen, Y .

NATURE, 2005, 437 (7063) :1299-1320

[2]

[Anonymous], 1999, Definition, diagnosis, and classification of diabetes mellitus and its complications: report of a WHO consultation

[3] Genetic signatures of strong recent positive selection at the lactase gene [J].

Bersaglieri, T ;

Sabeti, PC ;

Patterson, N ;

Vanderploeg, T ;

Schaffner, SF ;

Drake, JA ;

Rhodes, M ;

Reich, DE ;

Hirschhorn, JN .

AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (06) :1111-1120

[4] Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls [J].

Burton, Paul R. ;

Clayton, David G. ;

Cardon, Lon R. ;

Craddock, Nick ;

Deloukas, Panos ;

Duncanson, Audrey ;

Kwiatkowski, Dominic P. ;

McCarthy, Mark I. ;

Ouwehand, Willem H. ;

Samani, Nilesh J. ;

Todd, John A. ;

Donnelly, Peter ;

Barrett, Jeffrey C. ;

Davison, Dan ;

Easton, Doug ;

Evans, David ;

Leung, Hin-Tak ;

Marchini, Jonathan L. ;

Morris, Andrew P. ;

Spencer, Chris C. A. ;

Tobin, Martin D. ;

Attwood, Antony P. ;

Boorman, James P. ;

Cant, Barbara ;

Everson, Ursula ;

Hussey, Judith M. ;

Jolley, Jennifer D. ;

Knight, Alexandra S. ;

Koch, Kerstin ;

Meech, Elizabeth ;

Nutland, Sarah ;

Prowse, Christopher V. ;

Stevens, Helen E. ;

Taylor, Niall C. ;

Walters, Graham R. ;

Walker, Neil M. ;

Watkins, Nicholas A. ;

Winzer, Thilo ;

Jones, Richard W. ;

McArdle, Wendy L. ;

Ring, Susan M. ;

Strachan, David P. ;

Pembrey, Marcus ;

Breen, Gerome ;

St Clair, David ;

Caesar, Sian ;

Gordon-Smith, Katherine ;

Jones, Lisa ;

Fraser, Christine ;

Green, Elain K. .

NATURE, 2007, 447 (7145) :661-678

[5] Microsatellite variation and evolution of human lactase persistence [J].

Coelho, M ;

Luiselli, D ;

Bertorelle, G ;

Lopes, AI ;

Seixas, S ;

Destro-Bisol, G ;

Rocha, J .

HUMAN GENETICS, 2005, 117 (04) :329-339

[6] Efficiency and power in genetic association studies [J].

de Bakker, PIW ;

Yelensky, R ;

Pe'er, I ;

Gabriel, SB ;

Daly, MJ ;

Altshuler, D .

NATURE GENETICS, 2005, 37 (11) :1217-1223

[7] Increasing prevalence of diabetes mellitus and impaired glucose tolerance among 60-year-old Danes [J].

Drivsholm, T ;

Ibsen, H ;

Schroll, M ;

Davidsen, M ;

Borch-Johnsen, K .

DIABETIC MEDICINE, 2001, 18 (02) :126-132

[8] Association testing of common variants in the insulin receptor substrate-1 gene (IRS1) with type 2 diabetes [J].

Florez, J. C. ;

Sjogren, M. ;

Agapakis, C. M. ;

Burtt, N. P. ;

Almgren, P. ;

Lindblad, U. ;

Berglund, G. ;

Tuomi, T. ;

Gaudet, D. ;

Daly, M. J. ;

Ardlie, K. G. ;

Hirschhorn, J. N. ;

Altshuler, D. ;

Groop, L. .

DIABETOLOGIA, 2007, 50 (06) :1209-1217

[9] Sample size requirements for association studies of gene-gene interaction [J].

Gauderman, WJ .

AMERICAN JOURNAL OF EPIDEMIOLOGY, 2002, 155 (05) :478-484

[10] DETERMINANTS OF DISEASE AND DISABILITY IN THE ELDERLY - THE ROTTERDAM ELDERLY STUDY [J].

HOFMAN, A ;

GROBBEE, DE ;

DEJONG, PTVM ;

VANDENOUWELAND, FA .

EUROPEAN JOURNAL OF EPIDEMIOLOGY, 1991, 7 (04) :403-422

← 1 2 3 →