Question

Considerable effort has been directed toward determining the genes in which sequence variation contributes to the development of type 2 diabetes, a disease that results from a loss of sensitivity of cells to insulin. Approximately 800 genes have been implicated. Explain the significance of the observation.

Answer 1

Greater number of scientific efforts has been directed to determine the candidate genes responsible for type 2 diabetes (T2D). Systematic approaches like linkage studies, candidate gene studies and genome wide association studies has been performed to identify diabetes risk genes. The candidate gene and linkage-based studies could identify very few T2D risk genes whereas the genome-wide association studies has led to the identification of multiple genes, including several genes which were completely unknown regarding their involvement in T2D.

The following genetic variants are associated with type 2 diabetes are listed with genome-wide significance.

Locus	Chr	Risk allele frequency	OR (95%CI)
NOTCH2	1	0.11	1.13 (1.08-1.17)
PROX1	1	0.5	1.07 (1.05-1.09)
IRS1	2	0.61	1.19 (1.13-1.25)
THADA	2	0.92	1.15 (1.10-1.20)
RBMS1/ITGB6	2	0.57	1.11 (1.08-1.16)
BCL11A	2	0.46	1.08 (1.06-1.10)
GCKR	2	0.62	1.06 (1.04-1.08)
IGF2BP2	3	0.29	1.17 (1.10-1.25)
PPARG	3	0.92	1.14 (1.08-1.20)
ADCY5	3	0.78	1.12 (1.09-1.15)
ADAMTS9	3	0.81	1.09 (1.06-1.12)
WFS1	4	0.27	1.13 (1.07-1.18)
ZBED3	5	0.26	1.08 (1.06-1.11)
CDKAL1	6	0.31	1.12 (1.08-1.16)
JAZF1	7	0.52	1.10 (1.07-1.13)
GCK	7	0.2	1.07 (1.05-1.10)
KLF14	7	0.55	1.07 (1.05-1.10)
DGKB/TMEM195	7	0.47	1.06 (1.04-1.08)
SLC30A8	8	0.75	1.12 (1.07-1.16)
TP53INP1	8	0.48	1.06 (1.04-1.09)
CDKN2A/B	9	0.79	1.20 (1.14-1.25)
TLE4	9	0.93	1.11 (1.07-1.15)
TCF7L2	10	0.25	1.37 (1.28-1.47)
HHEX	10	0.56	1.13 (1.08-1.17)
CDC123/CAMK1D	10	0.23	1.11 (1.07-1.14)
KCNQ1	11	0.61	1.40 (1.34-1.47)
KCNJ11/ABCC8	11	0.5	1.15 (1.09-1.21)
CENTD2	11	0.88	1.14 (1.11-1.17)
MTNR1B	11	0.3	1.09 (1.06-1.12)
KCNQ1	11	0.52	1.08 (1.06-1.10)
HMGA2	12	0.1	1.10 (1.07-1.14)
TSPAN8/LGR5	12	0.23	1.09 (1.06-1.12)
OASL/HNF1A	12	0.85	1.07 (1.05-1.10)
PRC1	15	0.22	1.07 (1.05-1.09)
ZFAND6	15	0.56	1.06 (1.04-1.08)
FTO	16	0.45	1.15 (1.09-1.22)
HNF1B	17	0.43	1.12 (1.07-1.18)
DUSP9	X	0.12	1.27 (1.18-1.37)

Taken from-Ali, Omar. "Genetics of type 2 diabetes." World journal of diabetes 4.4 (2013): 114.

The significance of finding such genetic bariance responsible for pathogenesis of T2D would one day lead to better prediction, finding new drug targets and improve drug therapy.