Exploratory Bivariate Genome-Wide Analysis in Northern Chinese Twins Suggests Potential Loci at 2q33.1 Harboring...

Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) frequently coexist, yet the shared genetic variants underlying these conditions remain poorly understood. This study aimed to investigate shared genetic variants underlying lung function and glucose levels in middle-aged Chinese twins.

In this exploratory analysis, we reanalyzed genotype data from a previously published northern Chinese twin sample, including 139 dizygotic and 238 monozygotic twin pairs from the Qingdao Twin Registry. Lung function traits (FEV1, FVC, and FEV1/FVC) and fasting plasma glucose (FPG) were jointly analyzed using a twin-based bivariate genome-wide association approach, followed by functional annotation and gene-based analyses. Variants showing suggestive associations were further examined in an independent UK Biobank Chinese sample.

A significant negative correlation between the FEV1/FVC ratio and FPG was revealed. The analysis identified 29 SNPs reaching genome-wide significance, with association signals primarily clustering at the 2q33.1 locus. Functional annotation indicated that most associated variants were non-coding, with several SNPs overlapping regulatory elements annotated to the SPATS2L locus. Gene-based analysis further supported the involvement of SPATS2L in the shared genetic architecture of the two traits. In the validation analysis, seven variants at the 2q33.1 locus showed nominal associations with consistent effect directions.

This exploratory bivariate analysis provides evidence supporting shared genetic variants underlying pulmonary function and glucose regulation and offers insight into the genetic basis of COPD-T2DM comorbidity.