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Genetic association analysis of LARS2 with type 2 diabetes

Reiling, E.; Jafar-Mohammadi, B.; van't Riet, E.; Weedon, M. N.; van Vliet-Ostaptchouk, J. V.; Hansen, T.; Saxena, R.; van Haeften, T. W.; Arp, P. A. and Das, S., et al. (2010) In Diabetologia 53(1). p.103-110
Abstract
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... (More)
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. (Less)
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publication status
published
subject
keywords
Type 2 diabetes, SNP, Mitochondria, Genetics, LARS2
in
Diabetologia
volume
53
issue
1
pages
103 - 110
publisher
Springer Verlag
external identifiers
  • wos:000272530600015
  • scopus:72449147187
ISSN
1432-0428
DOI
10.1007/s00125-009-1557-7
language
English
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yes
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0103dfb2-220e-4368-a161-d28266ea8432 (old id 1535606)
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2010-01-27 11:49:28
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2018-05-29 12:15:38
@article{0103dfb2-220e-4368-a161-d28266ea8432,
  abstract     = {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.},
  author       = {Reiling, E. and Jafar-Mohammadi, B. and van't Riet, E. and Weedon, M. N. and van Vliet-Ostaptchouk, J. V. and Hansen, T. and Saxena, R. and van Haeften, T. W. and Arp, P. A. and Das, S. and Nijpels, G. and Groenewoud, M. J. and van Hove, E. C. and Uitterlinden, A. G. and Smit, J. W. A. and Morris, A. D. and Doney, A. S. F. and Palmer, C. N. A. and Guiducci, C. and Hattersley, A. T. and Frayling, T. M. and Pedersen, O. and Slagboom, P. E. and Altshuler, D. M. and Groop, Leif and Romijn, J. A. and Maassen, J. A. and Hofker, M. H. and Dekker, J. M. and McCarthy, M. I. and 't Hart, L. M.},
  issn         = {1432-0428},
  keyword      = {Type 2 diabetes,SNP,Mitochondria,Genetics,LARS2},
  language     = {eng},
  number       = {1},
  pages        = {103--110},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Genetic association analysis of LARS2 with type 2 diabetes},
  url          = {http://dx.doi.org/10.1007/s00125-009-1557-7},
  volume       = {53},
  year         = {2010},
}