Type 2 Diabetes, Obesity, growth & reproductive ageing genetics

BIOMARKERS

Below you can find links to our main publications on the genetics of biomarkers. Understanding the genetics of biomarkers including those circulating in the blood helps us make progress on disease aetiology and disease prediction. Because they are often highly genetic traits, they can also be useful in understanding genetic architecture. This work is led by Drs Andy Wood, Jess Tyrrell and Hanieh Yaghootkar, and Profs Michael Weedon and Tim Frayling

2016

Coming soon

2015

Wood AR, Tuke MA, Nalls M, Hernandez D, Gibbs JR, Lin H, Xu CS, Li Q, Shen J, Jun G, Almeida M, Tanaka T, Perry JR, Gaulton K, Rivas M, Pearson R, Curran JE,Johnson MP, Göring HH, Duggirala R, Blangero J, Mccarthy MI, Bandinelli S, Murray A, Weedon MN, Singleton A, Melzer D, Ferrucci L, Frayling TM.
Whole-genome sequencing to understand the genetic architecture of common gene expression and biomarker phenotypes.
Hum Mol Genet. 2015 Mar 1;24(5):1504-12. doi: PubMed Central PMCID:PMC4321449.

2014

Wood AR, Tuke MA, Nalls MA, Hernandez DG, Bandinelli S, Singleton AB, Melzer D, Ferrucci L, Frayling TM*, Weedon MN*.
Another explanation for apparent epistasis. Brief Communication arising
Nature. 2014 Oct 2;514(7520):E3-5. PMID: 25279928.

Yaghootkar H, Scott RA, White CC, Zhang W, Speliotes E, Munroe PB, Ehret GB, Bis JC, Fox CS, Walker M, Borecki IB, Knowles JW, Yerges-Armstrong L, Ohlsson C, Perry JR, Chambers JC, Kooner JS, Franceschini N, Langenberg C, Hivert MF,Dastani Z, Richards JB, Semple RK, Frayling TM.
Genetic evidence for a normal-weight “metabolically obese” phenotype linking insulin resistance,hypertension, coronary artery disease and type 2 diabetes.
Diabetes. 2014 Jul 21. PMID: 25048195.

2013

Westra HJ, Peters MJ, Esko T, Yaghootkar H, Schurmann C, Kettunen J, Christiansen MW, Fairfax BP, Schramm K, Powell JE, Zhernakova A, Zhernakova DV, Veldink JH, Van den Berg LH, Karjalainen J, Withoff S, Uitterlinden AG, Hofman A, Rivadeneira F, ‘t Hoen PA, Reinmaa E, Fischer K, Nelis M, Milani L, Melzer D, Ferrucci L, Singleton AB, Hernandez DG, Nalls MA, Homuth G, Nauck M, Radke D, Völker U, Perola M, Salomaa V, Brody J, Suchy-Dicey A, Gharib SA, Enquobahrie DA, Lumley T, Montgomery GW, Makino S, Prokisch H, Herder C, Roden M, Grallert H, Meitinger T, Strauch K, Li Y, Jansen RC, Visscher PM, Knight JC, Psaty BM, Ripatti S, Teumer A, Frayling TM, Metspalu A, van Meurs JB, Franke L.
Systematic identification of trans eQTLs as putative drivers of known disease associations.
Nature Genetics. 2013 Oct;45(10):1238-43 PMID: 24013639; PMCID: PMC3991562.

Yaghootkar H, Lamina C, Scott RA, Dastani Z, Hivert MF, Warren LL, Stancáková A, Buxbaum SG, Lyytikäinen LP, Henneman P, Wu Y, Cheung CY, Pankow JS, Jackson AU, Gustafsson S, Zhao JH, Ballantyne CM, Xie W, Bergman RN, Boehnke M, El Bouazzaoui F, Collins FS, Dunn SH, Dupuis J, Forouhi NG, Gillson C, Hattersley AT, Hong J, Kähönen M, Kuusisto J, Kedenko L, Kronenberg F, Doria A, Assimes TL, Ferrannini E, Hansen T, Hao K, Häring H, Knowles JW, Lindgren CM, Nolan JJ, Paananen J, Pedersen O, Quertermous T, Smith U; the GENESIS consortium; the RISC consortium, Lehtimäki T, Liu CT, Loos RJ, McCarthy MI, Morris AD, Vasan RS, Spector TD, Teslovich TM, Tuomilehto J, Willems van Dijk K, Viikari JS, Zhu N, Langenberg C, Ingelsson E, Semple RK, Sinaiko AR, Palmer CN, Walker M, Lam KS, Paulweber B, Mohlke KL, van Duijn C, Raitakari OT, Bidulescu A, Wareham NJ, Laakso M, Waterworth DM, Lawlor DA, Meigs JB, Richards JB, Frayling TM.
Mendelian Randomisation Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes.
Diabetes. 2013 Oct;62(10):3589-98.] PubMed PMID: 23835345.

Wood AR, Perry JR, Tanaka T, Hernandez DG, Zheng HF, Melzer D, Gibbs JR, Nalls MA, Weedon MN, Spector TD, Richards JB, Bandinelli S, Ferrucci L, Singleton AB, Frayling TM.
Imputation of variants from the 1000 Genomes Project modestly improves known associations and can identify low-frequency variant-phenotype associations undetected by HapMap based imputation.
PLoS One. 2013 May 16;8(5):e64343. PMC3655956.

Xie W, Wood AR, Lyssenko V, Weedon MN, Knowles JW, Alkayyali S, Assimes TL, Quertermous T, Abbasi F, Paananen J, Häring H, Hansen T, Pedersen O, Smith U, Laakso M; MAGIC Investigators; DIAGRAM Consortium; GENESIS Consortium; RISC Consortium, Dekker JM, Nolan JJ, Groop L, Ferrannini E, Adam KP, Gall WE, Frayling TM, Walker M.
Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes.
Diabetes. 2013 Jun;62(6):2141-50. PubMed PMID:23378610; PubMed Central PMCID: PMC3661655.

2012

Warren LL, Li L, Nelson MR, Ehm MG, Shen J, Fraser DJ, Aponte JL, Nangle KL, Slater AJ, Woollard PM, Hall MD, Topp SD, Yuan X, Cardon LR, Chissoe SL, Mooser V, Morris AD, Palmer CN, Perry JR, Frayling TM, Whittaker JC, Waterworth DM.
Deep resequencing unveils genetic architecture of ADIPOQ and identifies a novel low-frequency variant strongly associated with adiponectin variation.
Diabetes. 2012 May;61(5):1297-301. Epub 2012 Mar 8. PMCID: PMC3331741.

2011

Wood AR, Hernandez DG, Nalls MA, Yaghootkar H, Gibbs JR, Harries LW, Chong S, Moore M, Weedon MN, Guralnik JM, Bandinelli S, Murray A, Ferrucci L, Singleton AB, Melzer D, Frayling TM.
Allelic heterogeneity and more detailed analyses of known loci explain additional phenotypic variation and reveal complex patterns of association.
Hum Mol Genet. 2011 Jul 28.

Ohlsson C, Wallaschofski H, Lunetta KL, Stolk L, Perry JR, Koster A, Petersen AK, Eriksson J, Lehtimäki T, Huhtaniemi IT, Hammond GL, Maggio M, Coviello AD; EMAS Study Group, Ferrucci L, Heier M, Hofman A, Holliday KL, Jansson JO, Kähönen M, Karasik D, Karlsson MK, Kiel DP, Liu Y, Ljunggren O, Lorentzon M, Lyytikäinen LP, Meitinger T, Mellström D, Melzer D, Miljkovic I, Nauck M, Nilsson M, Penninx B, Pye SR, Vasan RS, Reincke M, Rivadeneira F, Tajar A, Teumer A, Uitterlinden AG, Ulloor J, Viikari J, Völker U, Völzke H, Wichmann HE, Wu TS, Zhuang WV, Ziv E, Wu FC, Raitakari O, Eriksson A, Bidlingmaier M, Harris TB, Murray A, de Jong FH, Murabito JM, Bhasin S, Vandenput L, Haring R.
Genetic determinants of serum testosterone concentrations in men.
PLoS Genet. 2011 Oct;7(10):e1002313. Epub 2011 Oct 6. PubMed Central PMCID: PMC3188559.

De Silva NM, Freathy RM, Palmer TM, Donnelly LA, Luan J, Gaunt T, Langenberg C, Weedon MN, Shields B, Knight BA, Ward KJ, Sandhu MS, Harbord RM, McCarthy MI, Smith GD, Ebrahim S, Hattersley AT, Wareham N, Lawlor DA, Morris AD, Palmer CN, Frayling TM.
Mendelian randomization studies do not support a role for raised circulating triglyceride levels influencing type 2 diabetes, glucose levels, or insulin resistance.
Diabetes. 2011 Mar;60(3):1008-18. PMCID: PMC3046819.

2010

Perry JR, Weedon MN, Langenberg C, Jackson AU, Lyssenko V, Sparsø T, Thorleifsson G, Grallert H, Ferrucci L, Maggio M, Paolisso G, Walker M, Palmer CN, Payne F, Young E, Herder C, Narisu N, Morken MA, Bonnycastle LL, Owen KR, Shields B, Knight B, Bennett A, Groves CJ, Ruokonen A, Jarvelin MR, Pearson E, Pascoe L, Ferrannini E, Bornstein SR, Stringham HM, Scott LJ, Kuusisto J, Nilsson P, Neptin M, Gjesing AP, Pisinger C, Lauritzen T, Sandbaek A, Sampson M, Zeggini ME, Lindgren CM, Steinthorsdottir V, Thorsteinsdottir U, Hansen T, Schwarz P, Illig T, Laakso M, Stefansson K, Morris AD, Groop L, Pedersen O, Boehnke M, Barroso I, Wareham NJ, Hattersley AT, McCarthy MI, Frayling TM.
Genetic evidence that raised sex hormone binding globulin (SHBG) levels reduce the risk of type 2
diabetes.
Hum Mol Genet. 2010 Feb 1;19(3):535-44. PMCID: PMC2798726.

2009

Shields BM, Freathy RM, Knight BA, Hill A, Weedon MN, Frayling TM, Hattersley AT, Vaidya B. Phosphodiesterase 8B gene polymorphism is associated with subclinical hypothyroidism in pregnancy.
J Clin Endocrinol Metab. 2009 Nov;94(11):4608-12. PMID: 19820008.

Perry JR, Ferrucci L, Bandinelli S, Guralnik J, Semba RD, Rice N, Melzer D; DIAGRAM Consortium, Saxena R, Scott LJ, McCarthy MI, Hattersley AT, Zeggini E, Weedon MN, Frayling TM.
Circulating beta-carotene levels and type 2 diabetes-cause or effect?
Diabetologia. 2009 Oct;52(10):2117-21. PMCID: PMC2746424.

Ferrucci L, Perry JR, Matteini A, Perola M, Tanaka T, Silander K, Rice N, Melzer D, Murray A, Cluett C, Fried LP, Albanes D, Corsi AM, Cherubini A, Guralnik J, Bandinelli S, Singleton A, Virtamo J, Walston J, Semba RD, Frayling TM.
Common variation in the beta-carotene 15,15′-monooxygenase 1 gene affects circulating levels of carotenoids: a genome-wide association study.
Am J Hum Genet. 2009 Feb;84(2):123-33. Epub 2009 Jan 29.

Webster RJ, Warrington NM, Weedon MN, Hattersley AT, McCaskie PA, Beilby JP, Palmer LJ, Frayling TM. The association of common genetic variants in the APOA5, LPL and GCK genes with longitudinal changes in metabolic and cardiovascular traits.
Diabetologia. 2009 Jan;52(1):106-14. Epub 2008 Nov 19.

2008

Yuan X, Waterworth D, Perry JR, Lim N, Song K, Chambers JC, Zhang W, Vollenweider P, Stirnadel H, Johnson T, Bergmann S, Beckmann ND, Li Y, Ferrucci L, Melzer D, Hernandez D, Singleton A, Scott J, Elliott P, Waeber G, Cardon L, Frayling TM, Kooner JS, Mooser V.
Population-based genome-wide association studies reveal six loci influencing plasma levels of liver enzymes.
Am J Hum Genet. 2008 Oct;83(4):520-8.

Panicker V, Cluett C, Shields B, Murray A, Parnell KS, Perry JR, Weedon MN, Singleton A, Hernandez D, Evans J, Durant C, Ferrucci L, Melzer D, Saravanan P, Visser TJ, Ceresini G, Hattersley AT, Vaidya B, Dayan CM, Frayling TM.
A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine.
J Clin Endocrinol Metab. 2008 Aug;93(8):3075-81. Epub 2008 May 20.

Melzer D, Perry JR, Hernandez D, Corsi AM, Stevens K, Rafferty I, Lauretani F, Murray A, Gibbs JR, Paolisso G, Rafiq S, Simon-Sanchez J, Lango H, Scholz S, Weedon MN, Arepalli S, Rice N, Washecka N, Hurst A, Britton A, Henley W, van de Leemput J, Li R, Newman AB, Tranah G, Harris T, Panicker V, Dayan C, Bennett A, McCarthy MI, Ruokonen A, Jarvelin MR, Guralnik J, Bandinelli S, Frayling TM*, Singleton A, Ferrucci L.
A genome-wide association study identifies protein quantitative trait loci (pQTLs).
PLoS Genet. 2008 May 9;4(5)

2007

Rafiq S, Stevens K, Hurst AJ, Murray A, Henley W, Weedon MN, Bandinelli S,
Corsi AM, Guralnik JM, Ferruci L, Melzer D, Frayling TM.

Common genetic variation in the gene encoding interleukin-1-receptor antagonist (IL-1RA) is associated with altered circulating IL-1RA levels.
Genes Immun. 2007 Jun;8(4):344-51.

Frayling TM, Rafiq S, Murray A, Hurst AJ, Weedon MN, Henley W, Bandinelli S, Corsi AM, Ferrucci L, Guralnik JM, Wallace RB, Melzer D.
An interleukin-18 polymorphism is associated with reduced serum concentrations and better physical functioning in older people.
J Gerontol A Biol Sci Med Sci. 2007 Jan;62(1):73-8.