1. Genetic association analysis of LARS2 with type 2 diabetes
- Author
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S. Das, Michael N. Weedon, Torben Hansen, J. V. van Vliet-Ostaptchouk, J. M. Dekker, Giel Nijpels, Alex S. F. Doney, André G. Uitterlinden, Johannes A Maassen, M. J. Groenewoud, E. C. van Hove, Erwin Reiling, T.W. van Haeften, Richa Saxena, Leif Groop, Marten H. Hofker, Johannes A. Romijn, P. E. Slagboom, Andrew D. Morris, Oluf Pedersen, Jan W. A. Smit, P. A. Arp, Colin N. A. Palmer, Mark I. McCarthy, Leen M 't Hart, Bahram Jafar-Mohammadi, Timothy M. Frayling, Candace Guiducci, Andrew T. Hattersley, David Altshuler, E. van 't Riet, Epidemiology and Data Science, General practice, Internal medicine, EMGO - Lifestyle, overweight and diabetes, University of Groningen, Center for Liver, Digestive and Metabolic Diseases (CLDM), Vascular Ageing Programme (VAP), Department of Finance, Ophthalmology, Internal Medicine, and General Internal Medicine
- Subjects
SELECTION ,Linkage disequilibrium ,Endocrinology, Diabetes and Metabolism ,LOCI ,Genome-wide association study ,Type 2 diabetes ,DETERMINANTS ,Genetics LARS2 Mitochondria SNP Type 2 diabetes genome-wide association mellitus glucose replication loci determinants dysfunction population prevalence selection ,Linkage Disequilibrium ,Body Mass Index ,GLUCOSE ,Cohort Studies ,MELLITUS ,0302 clinical medicine ,Polymorphism (computer science) ,POPULATION ,Genetics ,0303 health sciences ,education.field_of_study ,LARS2 ,16. Peace & justice ,3. Good health ,Mitochondria ,PREVALENCE ,Population ,SNP ,030209 endocrinology & metabolism ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,Amino Acyl-tRNA Synthetases ,Mitochondrial Proteins ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal Medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,GENOME-WIDE ASSOCIATION ,education ,Aged ,030304 developmental biology ,medicine.disease ,DYSFUNCTION ,Minor allele frequency ,Amino Acid Substitution ,Diabetes Mellitus, Type 2 ,REPLICATION ,Genome-Wide Association Study - Abstract
Aims/hypothesis 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. Methods 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. Results 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). Conclusions/interpretation 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. Electronic supplementary material The online version of this article (doi:10.1007/s00125-009-1557-7) contains supplementary material, which is available to authorised users.
- Published
- 2010
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