Table 5 Literature evidence for involvement of ‘suggestive’ markers (or gene loci) with p-values of <1.0E-05 in the associated phenotype traits.

rs3767494/C1orf106

HbA1c

A systematic analysis of genetic loci of cross autoimmune disorders implicated role of c1orf106 gene in the etiology of Type 1 diabetes⁷².

rs17117722/[TRA, TRD]

WcHtR

Both the TRA and TRD genes are members of the class of T-Cell receptor proteins. T-cells play an important role in the immune adaptation to both obesity and malnutrition⁷³. T-cells play an early and critical role in inducing inflammation in obesity and in the accumulation of inflammatory macrophages in obese adipose tissue; both these two processes are known to promote insulin resistance.

rs10005556/GAPDHP56

Weight/BMI/Waist Circumference

Genome region of GAPDHP56 (chr4:131448001-131451000, chr4:131449501-131452500) is reported as associated with total fat mass in genome-wide rare variants analysis of UK10K Cohorts⁵².

rs1184476/TEX29

Weight

Variants of TEX29 (alias C13orf16) are associated with age at menarche among Chinese women. However, as of now there is no report of their role in Weight gain⁵³.

rs9390649/UST

Waist circumference

A study using mice suggests an important role for Uronyl 2-sulfotransferase transfers in clearance of triglyceride-rich lipoprotein⁷⁴.

rs17639988/MDGA1, ZFAND3

HbA1c

Intergenic SNPs between MDGA1 and ZFAND3 are implicated in T2DM in East Asian population⁵⁴.

rs17716285/KSR1

HbA1c

Kinase suppressor of Ras 1 (KSR1) is required for Ras-mediated ERK pathway activation. This pathway is identified as modifiers of cellular insulin responsiveness. A study conducted on OLETF rat models for T2DM have shown that suppressing the KSR1/ERK complex brings down diabetic vascular complications⁵¹.

rs883431/SLC28A3

FPG

A study in rat indicates upregulation of SLC28A3 in glomerulus in diabetic condition. But till date no human study is reported⁴⁹.

rs4764409/PIK3C2G

FPG

Variants from this gene are found to be associated with high HbA1c and low serum insulin levels in Japanese T2D population⁵⁵. PI3K orchestrates its action through AKT2 pathway in the liver, as a main regulator of metabolism⁷⁵.

rs1800775/CETP

HDL

rs1800775 is a well-known upstream (~2KB) variant of CETP gene shown to be replicated in European population with HDL⁷⁶.

rs9326246/BUD13

TGL

Extended CARDIoGRAM study (involving participants of European ancestry) implicated rs9326246 marker as associated with TGL and as one of the important CAD susceptibility loci⁷⁶.

rs925530/TMEM120B

TGL

The role of TMEM120B in fat metabolism has been established in knockdown cell line studies⁵⁰.

rs17073574/LAMA4

TGL

Studies have shown association of LAMA4 in obesity and diabetic nephropathy^77,78.

rs11777524/LY6D, GML

TGL

There is lack of literature reports on the role of GML (Glycosylphosphatidylinositol-anchored molecule like) in processes relating to triglyceride. But there is evidence for GPIHBP1 (Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1) in causing hypertriglyceridemia. Protein sequence comparison analysis shows 28% identity between these two proteins. Furthermore, it is known that GPIHBP1 evolved LY6-like genes⁷⁹.

rs11602685/MICAL2

TGL

Its association with plasma uric acid in obese individuals is evident. However, it requires more literature support to establish its functional role in elevation of triglyceride levels⁸⁰.

rs10497520/TTN

SBP

Involvement of the TTN gene in hypertension is substantiated by literature evidences. Rain et al.⁸¹ found that phosphorylation of titin in right ventricular tissue was significantly reduced in pulmonary arterial hypertension patients (undergoing heart/lung transplantation) as compared with control subjects. Mutations in this gene are associated with familial hypertrophic cardiomyopathy⁸². Further, Ottenheijm et al. demonstrated that alternative splicing of the TTN gene was associated with diaphragm dysfunction in patients with mild to moderate chronic obstructive pulmonary disease⁸³.