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(1) Background and objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality throughout the world. In addition to genetics, increasing evidence suggests that Vitamin D (VitD) might be involved in different pathogenic mechanisms in COPD. Furthermore, the prevalence of VitD insufficiency is exceptionally high in COPD patients and increases with the severity. Based on the above, we first tested the relation between the top 10 single nucleotide polymorphisms from genome-wide association studies and the risk of COPD. Then, we investigated whether VitD levels might also have a role in COPD. A meta-analysis followed, combining our participants with previously published European and non-European populations (15,716 cases and 48,107 controls). (2) Methods: 631 Lebanese participants were recruited, of which ~28% were affected with COPD. Demographic and clinical data were collected, and DNA was genotyped using Kompetitive allele-specific PCR (KASPT M ). Adjusted multiple logistic regression models were used. Bonferroni corrections were also applied. The statistical power was also assessed. (3) Results: Both rs6837671A&gt;G in FAM13A and VitD levels were significantly associated with increased risk of COPD (OR = 1.75, p = 0.01, and OR = 3.10, p &lt; 0.001 respectively). An interaction between rs6837671A&gt;G in FAM13A and VitD levels, which increased COPD risk, was found (OR = 3.35 and p &lt; 0.001). The meta-analysis showed that rs6837671G increases COPD risk in populations from different origins; Europeans, Asians, and now in Middle-Eastern. (4) Conclusions: Our results suggest that rs6837671A&gt;G in FAM13A is a trans-ethnic genetic variant that interact with VitD to affect COPD.

rs6837671A>G in FAM13A Is a Trans-Ethnic Genetic Variant Interacting with Vitamin D Levels to Affect Chronic Obstructive Pulmonary Disease