TY - JOUR
T1 - A Perception on Genome-Wide Genetic Analysis of Metabolic Traits in Arab Populations
AU - Hebbar, Prashantha
AU - Abubaker, Jehad Ahmed
AU - Abu-Farha, Mohamed
AU - Tuomilehto, Jaakko
AU - Al-Mulla, Fahd
AU - Thanaraj, Alphonse Thangavel
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Despite dedicated nation-wide efforts to raise awareness against the harmful effects of fast-food consumption and sedentary lifestyle, the Arab population continues to struggle with an increased risk for metabolic disorders. Unlike the European population, the Arab population lacks well-established genetic risk determinants for metabolic disorders, and the transferability of established risk loci to this population has not been satisfactorily demonstrated. The most recent findings have identified over 240 genetic risk loci (with ~400 independent association signals) for type 2 diabetes, but thus far only 25 risk loci (
ADAMTS9, ALX4,
BCL11A, CDKAL1, CDKN2A/B, COL8A1,
DUSP9, FTO, GCK, GNPDA2, HMG20A, HNF1A, HNF1B, HNF4A, IGF2BP2, JAZF1, KCNJ11, KCNQ1, MC4R, PPARγ
, SLC30A8, TCF7L2, TFAP2B, TP53INP1, and
WFS1) have been replicated in Arab populations. To our knowledge, large-scale population- or family-based association studies are non-existent in this region. Recently, we conducted genome-wide association studies on Arab individuals from Kuwait to delineate the genetic determinants for quantitative traits associated with anthropometry, lipid profile, insulin resistance, and blood pressure levels. Although these studies led to the identification of novel recessive variants, they failed to reproduce the established loci. However, they provided insights into the genetic architecture of the population, the applicability of genetic models based on recessive mode of inheritance, the presence of genetic signatures of inbreeding due to the practice of consanguinity, and the pleiotropic effects of rare disorders on complex metabolic disorders. This perspective presents analysis strategies and study designs for identifying genetic risk variants associated with diabetes and related traits in Arab populations.
AB - Despite dedicated nation-wide efforts to raise awareness against the harmful effects of fast-food consumption and sedentary lifestyle, the Arab population continues to struggle with an increased risk for metabolic disorders. Unlike the European population, the Arab population lacks well-established genetic risk determinants for metabolic disorders, and the transferability of established risk loci to this population has not been satisfactorily demonstrated. The most recent findings have identified over 240 genetic risk loci (with ~400 independent association signals) for type 2 diabetes, but thus far only 25 risk loci (
ADAMTS9, ALX4,
BCL11A, CDKAL1, CDKN2A/B, COL8A1,
DUSP9, FTO, GCK, GNPDA2, HMG20A, HNF1A, HNF1B, HNF4A, IGF2BP2, JAZF1, KCNJ11, KCNQ1, MC4R, PPARγ
, SLC30A8, TCF7L2, TFAP2B, TP53INP1, and
WFS1) have been replicated in Arab populations. To our knowledge, large-scale population- or family-based association studies are non-existent in this region. Recently, we conducted genome-wide association studies on Arab individuals from Kuwait to delineate the genetic determinants for quantitative traits associated with anthropometry, lipid profile, insulin resistance, and blood pressure levels. Although these studies led to the identification of novel recessive variants, they failed to reproduce the established loci. However, they provided insights into the genetic architecture of the population, the applicability of genetic models based on recessive mode of inheritance, the presence of genetic signatures of inbreeding due to the practice of consanguinity, and the pleiotropic effects of rare disorders on complex metabolic disorders. This perspective presents analysis strategies and study designs for identifying genetic risk variants associated with diabetes and related traits in Arab populations.
KW - Arab population
KW - Epigenetics
KW - Euro-centric risk variants
KW - Genetics
KW - Genome-wide association studies
KW - Kuwait
KW - Risk loci
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85064200926&partnerID=8YFLogxK
U2 - 10.3389/fendo.2019.00008
DO - 10.3389/fendo.2019.00008
M3 - Article
C2 - 30761081
VL - 10
SP - 8
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
IS - JAN
ER -