Type 2 diabetes risk allele loci in the Qatari population

Sarah L. O'Beirne, Jacqueline Salit, Juan L. Rodriguez-Flores, Michelle R. Staudt, Charbel Abi Khalil, Khalid Adnan Mohamed A. Fakhro, Amal Robay, Monica D. Ramstetter, Iman Al Azwani, Joel Malek, Mahmoud Zirie, Amin Jayyousi, Ramin Badii, Ajayeb Al-Nabet Al-marri, Maria J. Chiuchiolo, Alya Al-Shakaki, Omar Chidiac, Maey Gharbiah, Abdulbari Bener, Dora StadlerNeil R. Hackett, Jason G. Mezey, Ronald Crystal

Research output: Contribution to journalArticle

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Abstract

Background: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. Methods: All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations. Results: Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. Conclusions: With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians.

Original languageEnglish
Article numbere0156834
JournalPLoS One
Volume11
Issue number7
DOIs
Publication statusPublished - 1 Jul 2016

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Medical problems
noninsulin-dependent diabetes mellitus
Type 2 Diabetes Mellitus
Alleles
Polymorphism
alleles
single nucleotide polymorphism
Single Nucleotide Polymorphism
loci
Nucleotides
Population
Haplotypes
haplotypes
odds ratio
T Cell Transcription Factor 1
risk factors
Odds Ratio
Middle East
Population Genetics
Population Density

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Type 2 diabetes risk allele loci in the Qatari population. / O'Beirne, Sarah L.; Salit, Jacqueline; Rodriguez-Flores, Juan L.; Staudt, Michelle R.; Abi Khalil, Charbel; Fakhro, Khalid Adnan Mohamed A.; Robay, Amal; Ramstetter, Monica D.; Al Azwani, Iman; Malek, Joel; Zirie, Mahmoud; Jayyousi, Amin; Badii, Ramin; Al-Nabet Al-marri, Ajayeb; Chiuchiolo, Maria J.; Al-Shakaki, Alya; Chidiac, Omar; Gharbiah, Maey; Bener, Abdulbari; Stadler, Dora; Hackett, Neil R.; Mezey, Jason G.; Crystal, Ronald.

In: PLoS One, Vol. 11, No. 7, e0156834, 01.07.2016.

Research output: Contribution to journalArticle

O'Beirne, SL, Salit, J, Rodriguez-Flores, JL, Staudt, MR, Abi Khalil, C, Fakhro, KAMA, Robay, A, Ramstetter, MD, Al Azwani, I, Malek, J, Zirie, M, Jayyousi, A, Badii, R, Al-Nabet Al-marri, A, Chiuchiolo, MJ, Al-Shakaki, A, Chidiac, O, Gharbiah, M, Bener, A, Stadler, D, Hackett, NR, Mezey, JG & Crystal, R 2016, 'Type 2 diabetes risk allele loci in the Qatari population', PLoS One, vol. 11, no. 7, e0156834. https://doi.org/10.1371/journal.pone.0156834
O'Beirne SL, Salit J, Rodriguez-Flores JL, Staudt MR, Abi Khalil C, Fakhro KAMA et al. Type 2 diabetes risk allele loci in the Qatari population. PLoS One. 2016 Jul 1;11(7). e0156834. https://doi.org/10.1371/journal.pone.0156834
O'Beirne, Sarah L. ; Salit, Jacqueline ; Rodriguez-Flores, Juan L. ; Staudt, Michelle R. ; Abi Khalil, Charbel ; Fakhro, Khalid Adnan Mohamed A. ; Robay, Amal ; Ramstetter, Monica D. ; Al Azwani, Iman ; Malek, Joel ; Zirie, Mahmoud ; Jayyousi, Amin ; Badii, Ramin ; Al-Nabet Al-marri, Ajayeb ; Chiuchiolo, Maria J. ; Al-Shakaki, Alya ; Chidiac, Omar ; Gharbiah, Maey ; Bener, Abdulbari ; Stadler, Dora ; Hackett, Neil R. ; Mezey, Jason G. ; Crystal, Ronald. / Type 2 diabetes risk allele loci in the Qatari population. In: PLoS One. 2016 ; Vol. 11, No. 7.
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abstract = "Background: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. Methods: All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22{\%}), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations. Results: Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. Conclusions: With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians.",
author = "O'Beirne, {Sarah L.} and Jacqueline Salit and Rodriguez-Flores, {Juan L.} and Staudt, {Michelle R.} and {Abi Khalil}, Charbel and Fakhro, {Khalid Adnan Mohamed A.} and Amal Robay and Ramstetter, {Monica D.} and {Al Azwani}, Iman and Joel Malek and Mahmoud Zirie and Amin Jayyousi and Ramin Badii and {Al-Nabet Al-marri}, Ajayeb and Chiuchiolo, {Maria J.} and Alya Al-Shakaki and Omar Chidiac and Maey Gharbiah and Abdulbari Bener and Dora Stadler and Hackett, {Neil R.} and Mezey, {Jason G.} and Ronald Crystal",
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T1 - Type 2 diabetes risk allele loci in the Qatari population

AU - O'Beirne, Sarah L.

AU - Salit, Jacqueline

AU - Rodriguez-Flores, Juan L.

AU - Staudt, Michelle R.

AU - Abi Khalil, Charbel

AU - Fakhro, Khalid Adnan Mohamed A.

AU - Robay, Amal

AU - Ramstetter, Monica D.

AU - Al Azwani, Iman

AU - Malek, Joel

AU - Zirie, Mahmoud

AU - Jayyousi, Amin

AU - Badii, Ramin

AU - Al-Nabet Al-marri, Ajayeb

AU - Chiuchiolo, Maria J.

AU - Al-Shakaki, Alya

AU - Chidiac, Omar

AU - Gharbiah, Maey

AU - Bener, Abdulbari

AU - Stadler, Dora

AU - Hackett, Neil R.

AU - Mezey, Jason G.

AU - Crystal, Ronald

PY - 2016/7/1

Y1 - 2016/7/1

N2 - Background: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. Methods: All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations. Results: Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. Conclusions: With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians.

AB - Background: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians. Methods: All subjects were ≥3 generation Qataris. Cases with T2D (n = 1,124) and controls (n = 590) were randomly recruited and assigned to the 3 known Qatari genetic subpopulations [Bedouin (Q1), Persian/South Asian (Q2) and African (Q3)]. Subjects underwent genotyping for 37 single nucleotide polymorphisms (SNPs) in 29 genes known to be associated with T2D in Europeans and/or Asian populations, and an additional 27 tag SNPs related to these susceptibility loci. Pre-study power analysis suggested that with the known incidence of T2D in adult Qataris (22%), the study population size would be sufficient to detect significant differences if the SNPs were risk factors among Qataris, assuming that the odds ratio (OR) for T2D SNPs in Qatari's is greater than or equal to the SNP with highest known OR in other populations. Results: Haplotype analysis demonstrated that Qatari haplotypes in the region of known T2D risk alleles in Q1 and Q2 genetic subpopulations were similar to European haplotypes. After Benjamini-Hochberg adjustment for multiple testing, only two SNPs (rs7903146 and rs4506565), both associated with transcription factor 7-like 2 (TCF7L2), achieved statistical significance in the whole study population. When T2D subjects and control subjects were assigned to the known 3 Qatari subpopulations, and analyzed individually and with the Q1 and Q2 genetic subpopulations combined, one of these SNPs (rs4506565) was also significant in the admixed group. No other SNPs associated with T2D in all Qataris or individual genetic subpopulations. Conclusions: With the caveats of the power analysis, the European/Asian T2D SNPs do not contribute significantly to the high prevalence of T2D in the Qatari population, suggesting that the genetic risks for T2D are likely different in Qataris compared to Europeans and Asians.

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