Stratifying type 2 diabetes cases by BMI identifies genetic risk variants in LAMA1 and enrichment for risk variants in lean compared to obese cases.
- Perry, JR
- Voight, BF
- Yengo, L
- Amin, N
- Dupuis, J
- Ganser, M
- Grallert, H
- Navarro, P
- Li, M
- Qi, L
- Steinthorsdottir, V
- Scott, RA
- Almgren, P
- Arking, DE
- Aulchenko, Y
- Balkau, B
- Benediktsson, R
- Bergman, RN
- Boerwinkle, E
- Bonnycastle, L
- Burtt, NP
- Campbell, H
- Charpentier, G
- Collins, FS
- Gieger, C
- Green, T
- Hadjadj, S
- Hattersley, AT
- Herder, C
- Hofman, A
- Johnson, AD
- Kottgen, A
- Kraft, P
- Labrune, Y
- Langenberg, C
- Manning, AK
- Mohlke, KL
- Morris, AP
- Oostra, B
- Pankow, J
- Petersen, AK
- Pramstaller, PP
- Prokopenko, I
- Rathmann, W
- Rayner, W
- Roden, M
- Rudan, I
- Rybin, D
- Scott, LJ
- Sigurdsson, G
- Sladek, R
- Thorleifsson, G
- Thorsteinsdottir, U
- Tuomilehto, J
- Uitterlinden, AG
- Vivequin, S
- Weedon, MN
- Wright, AF
- Hu, FB
- Illig, T
- Kao, L
- Meigs, JB
- Wilson, JF
- Stefansson, K
- van Duijn, C
- Altschuler, D
- Morris, AD
- Boehnke, M
- McCarthy, MI
- Froguel, P
- Palmer, CN
- Wareham, NJ
- Groop, L
- Frayling, TM
- Cauchi, S
DOIAbstract
Common diseases such as type 2 diabetes are phenotypically heterogeneous. Obesity is a major risk factor for type 2 diabetes, but patients vary appreciably in body mass index. We hypothesized that the genetic predisposition to the disease may be different in lean (BMI<25 Kg/m²) compared to obese cases (BMI≥30 Kg/m²). We performed two case-control genome-wide studies using two accepted cut-offs for defining individuals as overweight or obese. We used 2,112 lean type 2 diabetes cases (BMI<25 kg/m²) or 4,123 obese cases (BMI≥30 kg/m²), and 54,412 un-stratified controls. Replication was performed in 2,881 lean cases or 8,702 obese cases, and 18,957 un-stratified controls. To assess the effects of known signals, we tested the individual and comb...
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