188-LB: Type 2 Diabetes Is Genetically Correlated with Multiple Long-Term Conditions but These Correlations Are Only Partly Explained by BMI Free

People with Type 2 diabetes (T2D) are at high risk of many other long term conditions (LTC). These LTCs include Osteoarthritis, Alzheimer’s disease and Depression as well as cardiovascular conditions but the causes of these higher risks are uncertain and hard to study in trials or observational studies. We aimed to use a genetic approach to test the hypothesis that type 2 diabetes shares disease pathways with other LTCs and that BMI would account for some of the sharing. We used data from large (14,000 - 120,000 cases) genome wide association studies to calculate genetic correlations (Rg) between T2D and 16 LTCs. We then used Genomic structural equation models to test the extent to which the genetic component to BMI accounted for the correlations. This genetic approach has the advantage that type 2 diabetes can be compared to co-morbidities across databases. Eight of 16 LTCs were genetically correlated (Rg) with T2D. These were Heart failure (HF; Rg 0.49, p=1x10^-50), coronary artery disease (CAD; 0.40, p=6x10^-75), gastroesophageal reflux (GORD, 0.36, p=3x10^-58), stroke (0.32, p=4x10^-20), osteoarthritis (OA; 0.32, p=4x10^-28), depression (0.14, p=4x10^-11), hearing aid use (0.13, p=2x10^-3) and asthma (0.13, p=9x10^-9). The genetic component to BMI accounted for a large proportion of the genetic correlations between T2D and osteoarthritis (87% of Rg), hearing aid use (68%) and asthma (64%), but a smaller proportion of T2D’s genetic correlations with stroke (32%), CAD (35%), HF (47%), depression (39%) and GORD (44%). T2D shares a genetic component with multiple long term conditions and excess body weight is only partly responsible. We hypothesize that where the genetic correlation between T2D and another LTC dramatically diminishes upon adjustment for BMI, lifestyle interventions on BMI may successfully reduce the burden of both LTCs. Where there is less such attenuation, alternative risk factors, such as body fat distribution, need to be considered.