Excess Heritability Contribution of Alcohol Consumption Variants in the “Missing Heritability” of Type 2 Diabetes Mellitus

We aim to compare the relative heritability contributed by variants of behavior-related environmental phenotypes and elucidate the role of these factors in the conundrum of “missing heritability” of type 2 diabetes. Methods: We used Linkage-Disequilibrium Adjusted Kinships (LDAK) and LDAK-Thin models to calculate the relative heritability of each variant and compare the relative heritability for each phenotype. Biological analysis was carried out for the phenotype whose variants made a significant contribution. Potential hub genes were prioritized based on topological parameters of the protein-–protein interaction network. We included 16 behavior-related phenotypes and 2607 valid variants. In the LDAK model, we found the variants of alcohol consumption and caffeine intake were identified as contributing higher relative heritability than that of the random variants. Compared with the relative expected heritability contributed by the variants associated with type 2 diabetes, the relative expected heritability contributed by the variants associated with these two phenotypes was higher. In the LDAK-Thin model, the relative heritability of variants of 11 phenotypes was statistically higher than random variants. Biological function analysis showed the same distributions among type 2 diabetes and alcohol consumption. We eventually screened out 31 hub genes interacting intensively, four of which were validated and showed the upregulated expression pattern in blood samples seen in type 2 diabetes cases. Conclusion: We found that alcohol consumption contributed higher relative heritability. Hub genes may influence the onset of type 2 diabetes by a mediating effect or a pleiotropic effect. Our results provide new insight to reveal the role of behavior-related factors in the conundrum of “missing heritability” of type 2 diabetes.

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Indian consensus on durability of glycemic control in type 2 diabetes management and role of oral antidiabetic drugs

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20214733 ◽

2021 ◽

Vol 9 (12) ◽

pp. 3745

Author(s):

Manoj Chawla ◽

Pramila Kalra ◽

A. K. Khanna ◽

Sisir Kumar Mahapatro

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Combination Therapy ◽

Diabetes Management ◽

Antidiabetic Drugs ◽

Oral Antidiabetic Drugs ◽

Related Factors ◽

Oral Antidiabetic

The prevalence of type 2 diabetes mellitus (T2DM) is increasing in an alarming way in India as well as across the globe. In order to minimize complications, there is a need to maintain good glycemic control in patients with T2DM and long-term durable glycemic control remains a challenge. Clinically, this challenge was addressed by step-wise intensification of therapy with additional antidiabetic drugs to maintain glycemic control. Various disease and patient-related factors as well as different antidiabetic agents influenced the durability of glycemic control differently. While understanding of the factors that influenced therapeutic outcomes had evolved, there was paucity of information about the durability of glycemic control and the role of oral antidiabetic drugs (OADs) in achieving it. With an objective to understand the role of durability of glycemic response in the management of Indian patients with T2DM, 4 advisory board meetings attended by 48 physicians from across the country were conducted in Mumbai, Delhi, Kolkata and Bengaluru. There was consensus to consider durability of glycemic control as an important goal in the management of T2DM. Personalized approach in T2DM management along with early initiation of dual combination therapy were recommended to achieve durability. Age group of patients, body mass index, glycated hemoglobin levels at diagnosis, presence or absence of comorbidities and complications are important factors that need to be considered before initiating dual combination therapy for patients with T2DM.

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