Recent progress in the use of genetics to understand links between type 2 diabetes and related metabolic traits

Table 1 Evidence for links between diabetes and related metabolic traits from genetic studies

Primary trait	Secondary trait	Loci	Result	Reference(s)
Fasting glucose in the normal range	Type 2 diabetes	GCK and MTN1RBG6PC2	Variants at these loci have the strongest effects on fasting glucose but relatively small effects on risk of type 2 diabetesFasting glucose increasing allele is paradoxically associated with improved response to an oral glucose challenge	[14, 18, 20]
Circadian rhythm	Insulin secretion	MTN1RB	Variants in the melatonin receptor MTNR1B are associated with increased fasting glucose, impairment of insulin secretion from the pancreatic beta cell, and increased risk of type 2 diabetes	[2, 23, 26]
Inflammatory marker CRP	Obesity and metabolic syndrome phenotypes	CRP	CRP has no causal effect on obesity and development of insulin resistance and type 2 diabetes, suggesting inflammation is not causally linked to obesity	[28, 44]
BMI	Circulating CRP	FTO	Obesity causally affects the circulating levels of CRP	[28]
SHBG levels	Type 2 diabetes	SHBG	Raised circulating SHBG levels reduce the risk of type 2 diabetes	[35, 36]
Birth weight	Type 2 diabetes	CDKAL1, HHEX/IDE and ADCY5	Genetic variants that influence birth weight also influence type 2 diabetes risk	[40–42]

BMI, body mass index; CRP, C-reactive protein; SHBG, sex hormone binding globulin.

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