Adipose tissue communicates with other organs by secreting endocrine molecules known as adipocytokines, such as leptin, adiponectin, and resistin [1]. They play a pivotal role linking adiposity, insulin resistance, and inflammation [2]. Dysregulation of adipocytokines is strongly associated with metabolic disorders, including obesity and type 2 diabetes mellitus [[3], [4], [5]].

Leptin, a pro-inflammatory cytokine involved in appetite regulation and energy balance, also influences glucose metabolism [6]. Genetics account for 30–50 % of the variation in circulating leptin levels, regardless of adiposity. [[7], [8], [9]]. While candidate genetic studies have identified the role of LEP gene in regulating leptin levels, genome-wide association study of leptin in 52,140 individuals of European ancestry identified robust associations in genes LEP, SLC32A1, GCKR, CCNL1, and FTO [10]. Further, exome-based analysis of leptin in 57,232 individuals of diverse ancestries identified 5 novel associations in LEP, ZNF800, KLHL31, ACTL9, and KLF14 [11].

Adiponectin, an anti-inflammatory cytokine that enhances insulin sensitivity, has an estimated genetic heritability of 30–70 % [[12], [13], [14], [15]]. Both candidate genetic studies and GWAS on adiponectin levels have highlighted the association of variants in ADIPOQ gene [[16], [17], [18], [19]]. A recent cross-ancestry GWAS identified over 20 loci associated with adiponectin levels [20].

Resistin, another pro-inflammatory cytokine implicated in insulin resistance, is highly heritable (up to 70 %) and genetically correlated with insulin resistance [21,22]. Genetic studies have focused on the RETN gene, along with additional loci such as TYW3/CRYZ and NDST4 [23,24].

Given their critical roles in metabolic health, understanding the genetic regulation of adipocytokines is essential for elucidating the pathophysiology of obesity and related disorders. In this study, we present the sole genome-wide association study and an exome-wide association study (array-based), on childhood adipocytokines – leptin, adiponectin, and resistin in the South Asian population. A two-staged GWAS (N = 5258) was performed, along side an exome-wide single variant analysis of the common variants (N = 4387), and rare variant testing (N = 4578; NGenes = 9827). By exploring both common and rare variants, this study aims to uncover genetic factors regulating adipokine biology.