Louise K Metcalfe1, Mohanraj Krishnan2, Nigel Turner1, Hanieh Yaghootkar3, Troy L Merry4,5, Ofa Dewes5,6, Jennie Harré Hindmarsh7, Janak De Zoysa2,8, Nicola Dalbeth2, Lisa K Stamp9, Tony R Merriman5,10, Greg Smith1, Peter Shepherd5,6, Rinki Murphy11,12. 1. Department of Pharmacology, School of Medical Sciences, Faculty of Medicine, UNSW Sydney, Sydney, NSW, Australia. 2. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. 3. Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, UK. 4. Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand. 5. Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand. 6. Department of Molecular Medicine & Pathology, University of Auckland, Auckland, New Zealand. 7. Ngāti Porou Hauora Charitable Trust, Te Puia Springs, Tairāwhiti East Coast, New Zealand. 8. Renal Service, Waitemata District Health Board, Auckland, New Zealand. 9. Dept of Medicine, University of Otago, Christchurch, New Zealand. 10. Dept of Biochemistry, University of Otago, Dunedin, New Zealand. 11. Department of Medicine, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand. R.Murphy@auckland.ac.nz. 12. Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand. R.Murphy@auckland.ac.nz.
Abstract
BACKGROUND: The CREBRF missense variant (p.Arg457Gln) is paradoxically associated with lower risk of type 2 diabetes, yet higher body mass index (BMI). Here we sought to determine whether this CREBRF variant might be associated with adult height. METHODS: Linear regression was used to analyse the association of the CREBRF minor (A) allele with height in 2286 Māori and Pacific adults living in Aotearoa/New Zealand. A potential type 2 diabetes index event was corrected to account for a bias that may be the cause of paradoxical association between the CREBRF diabetes-protective allele and higher BMI and height. RESULTS: The CREBRF protective allele was associated with increased adult height (ß = 1.25 cm, P = 3.9 × 10-6), with the effect being more pronounced in males. The lower odds of diabetes remained similar when analyses were adjusted for height (OR = 0.67-0.65). We found no evidence of a diabetes index event bias to explain the paradoxical effect of CREBRF with either BMI or height and diabetes. The orthologous CREBRF p.Arg457Gln variant was created in knock-in mice to independently assess the effect of the variant, and length was found to be greater in male mice at 8 weeks of age. CONCLUSION: These data taken together indicate that CREBRF p.Arg457Gln is associated with taller stature in Māori and Pacific adults.
BACKGROUND: The CREBRF missense variant (p.Arg457Gln) is paradoxically associated with lower risk of type 2 diabetes, yet higher body mass index (BMI). Here we sought to determine whether this CREBRF variant might be associated with adult height. METHODS: Linear regression was used to analyse the association of the CREBRF minor (A) allele with height in 2286 Māori and Pacific adults living in Aotearoa/New Zealand. A potential type 2 diabetes index event was corrected to account for a bias that may be the cause of paradoxical association between the CREBRFdiabetes-protective allele and higher BMI and height. RESULTS: The CREBRF protective allele was associated with increased adult height (ß = 1.25 cm, P = 3.9 × 10-6), with the effect being more pronounced in males. The lower odds of diabetes remained similar when analyses were adjusted for height (OR = 0.67-0.65). We found no evidence of a diabetes index event bias to explain the paradoxical effect of CREBRF with either BMI or height and diabetes. The orthologous CREBRFp.Arg457Gln variant was created in knock-in mice to independently assess the effect of the variant, and length was found to be greater in male mice at 8 weeks of age. CONCLUSION: These data taken together indicate that CREBRFp.Arg457Gln is associated with taller stature in Māori and Pacific adults.
Authors: Hanieh Yaghootkar; Michael P Bancks; Sam E Jones; Aaron McDaid; Robin Beaumont; Louise Donnelly; Andrew R Wood; Archie Campbell; Jessica Tyrrell; Lynne J Hocking; Marcus A Tuke; Katherine S Ruth; Ewan R Pearson; Anna Murray; Rachel M Freathy; Patricia B Munroe; Caroline Hayward; Colin Palmer; Michael N Weedon; James S Pankow; Timothy M Frayling; Zoltán Kutalik Journal: Hum Mol Genet Date: 2017-03-01 Impact factor: 6.150
Authors: Jenna C Carlson; Samantha L Rosenthal; Emily M Russell; Nicola L Hawley; Guangyun Sun; Hong Cheng; Take Naseri; Muagututi'a S Reupena; John Tuitele; Ranjan Deka; Stephen T McGarvey; Daniel E Weeks; Ryan L Minster Journal: Am J Hum Biol Date: 2020-03-19 Impact factor: 1.937