Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene.
Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene.
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作者：
Zhao J;Li M;Bradfield JP;Wang K;Zhang H;Sleiman P;Kim CE;Annaiah K;Glaberson W;Glessner JT;Otieno FG;Thomas KA;Garris M;Hou C;Frackelton EC;Chiavacci RM;Berkowitz RI;Hakonarson H;Grant SF
许多研究发现，出生体重过轻与以后患2型糖尿病有关；然而，这种相关性的潜在机制仍未得到解决。最近，低出生体重与CDKAL1和HHEX-IDE位点的单核苷酸多态性（snp）之间存在关联，这两个位点以前与2型糖尿病的发病机制有关。为了研究2型糖尿病风险等位基因是否与低出生体重有关，我们检查了20个这样的基因位点对这一特征的影响。我们利用正在进行的一项全基因组关联研究的数据，对5,465名有出生体重记录的高加索儿童进行了研究，研究了先前报道的20个基因位点的2型糖尿病相关变异，包括TCF7L2、HHEX-IDE、PPARG、KCNJ11、SLC30A8、IGF2BP2、CDKAL1、CDKN2A/2B和JAZF1与出生体重的关系。我们的数据显示，CDKAL1位点上rs7756992的小等位基因（P = 8 × 10−5）与低出生体重密切相关，而先前在同一位点上的变异的完美替代仅产生了名义上显著的关联（P = 0.01; r2 rs7756992 = 0.677）。然而，没有发现与其他2型糖尿病基因座的关联。我们观察到低出生体重与CDKAL1位点的2型糖尿病风险等位基因之间的关联。我们的数据表明，在之前的研究中被确定为2型糖尿病标志物的同一基因位点也会影响出生体重。
A number of studies have found that reduced birth weight is associated with type 2 diabetes later in life; however, the underlying mechanism for this correlation remains unresolved. Recently, association has been demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 and HHEX-IDE loci, regions that were previously implicated in the pathogenesis of type 2 diabetes. In order to investigate whether type 2 diabetes risk–conferring alleles associate with low birth weight in our Caucasian childhood cohort, we examined the effects of 20 such loci on this trait. Using data from an ongoing genome-wide association study in our cohort of 5,465 Caucasian children with recorded birth weights, we investigated the association of the previously reported type 2 diabetes–associated variation at 20 loci including TCF7L2, HHEX-IDE, PPARG, KCNJ11, SLC30A8, IGF2BP2, CDKAL1, CDKN2A/2B, and JAZF1 with birth weight. Our data show that the minor allele of rs7756992 (P = 8 × 10−5) at the CDKAL1 locus is strongly associated with lower birth weight, whereas a perfect surrogate for variation previously implicated for the trait at the same locus only yielded nominally significant association (P = 0.01; r2 rs7756992 = 0.677). However, association was not detected with any of the other type 2 diabetes loci studied. We observe association between lower birth weight and type 2 diabetes risk–conferring alleles at the CDKAL1 locus. Our data show that the same genetic locus that has been identified as a marker for type 2 diabetes in previous studies also influences birth weight.
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影响因子：
30.8
作者：
Zeggini, Eleftheria;Scott, Laura J.;Saxena, Richa;Voight, Benjamin F.;Marchini, Jonathan L.;Hu, Tianle;de Bakker, Paul I. W.;Abecasis, Goncalo R.;Almgren, Peter;Andersen, Gitte;Ardlie, Kristin;Bostroem, Kristina Bengtsson;Bergman, Richard N.;Bonnycastle, Lori L.;Borch-Johnsen, Knut;Burtt, Noel P.;Chen, Hong;Chines, Peter S.;Daly, Mark J.;Deodhar, Parimal;Ding, Chia-Jen;Doney, Alex S. F.;Duren, William L.;Elliott, Katherine S.;Erdos, Michael R.;Frayling, Timothy M.;Freathy, Rachel M.;Gianniny, Lauren;Grallert, Harald;Grarup, Niels;Groves, Christopher J.;Guiducci, Candace;Hansen, Torben;Herder, Christian;Hitman, Graham A.;Hughes, Thomas E.;Isomaa, Bo;Jackson, Anne U.;Jorgensen, Torben;Kong, Augustine;Kubalanza, Kari;Kuruvilla, Finny G.;Kuusisto, Johanna;Langenberg, Claudia;Lango, Hana;Lauritzen, Torsten;Li, Yun;Lindgren, Cecilia M.;Lyssenko, Valeriya;Marvelle, Amanda F.;Meisinger, Christa;Midthjell, Kristian;Mohlke, Karen L.;Morken, Mario A.;Morris, Andrew D.;Narisu, Narisu;Nilsson, Peter;Owen, Katharine R.;Palmer, Colin N. A.;Payne, Felicity;Perry, John R. B.;Pettersen, Elin;Platou, Carl;Prokopenko, Inga;Qi, Lu;Qin, Li;Rayner, Nigel W.;Rees, Matthew;Roix, Jeffrey J.;Sandbaek, Anelli;Shields, Beverley;Sjogren, Marketa;Steinthorsdottir, Valgerdur;Stringham, Heather M.;Swift, Amy J.;Thorleifsson, Gudmar;Thorsteinsdottir, Unnur;Timpson, Nicholas J.;Tuomi, Tiinamaija;Tuomilehto, Jaakko;Walker, Mark;Watanabe, Richard M.;Weedon, Michael N.;Willer, Cristen J.;Illig, Thomas;Hveem, Kristian;Hu, Frank B.;Laakso, Markku;Stefansson, Kari;Pedersen, Oluf;Wareham, Nicholas J.;Barroso, Ines;Hattersley, Andrew T.;Collins, Francis S.;Groop, Leif;McCarthy, Mark I.;Boehnke, Michael;Altshuler, David
通讯作者：
Altshuler, David
影响因子：
30.8
作者：
Hattersley, AT;Beards, F;Ellard, S
通讯作者：
Ellard, S
影响因子：
30.8
作者：
Prokopenko I;Langenberg C;Florez JC;Saxena R;Soranzo N;Thorleifsson G;Loos RJ;Manning AK;Jackson AU;Aulchenko Y;Potter SC;Erdos MR;Sanna S;Hottenga JJ;Wheeler E;Kaakinen M;Lyssenko V;Chen WM;Ahmadi K;Beckmann JS;Bergman RN;Bochud M;Bonnycastle LL;Buchanan TA;Cao A;Cervino A;Coin L;Collins FS;Crisponi L;de Geus EJ;Dehghan A;Deloukas P;Doney AS;Elliott P;Freimer N;Gateva V;Herder C;Hofman A;Hughes TE;Hunt S;Illig T;Inouye M;Isomaa B;Johnson T;Kong A;Krestyaninova M;Kuusisto J;Laakso M;Lim N;Lindblad U;Lindgren CM;McCann OT;Mohlke KL;Morris AD;Naitza S;Orrù M;Palmer CN;Pouta A;Randall J;Rathmann W;Saramies J;Scheet P;Scott LJ;Scuteri A;Sharp S;Sijbrands E;Smit JH;Song K;Steinthorsdottir V;Stringham HM;Tuomi T;Tuomilehto J;Uitterlinden AG;Voight BF;Waterworth D;Wichmann HE;Willemsen G;Witteman JC;Yuan X;Zhao JH;Zeggini E;Schlessinger D;Sandhu M;Boomsma DI;Uda M;Spector TD;Penninx BW;Altshuler D;Vollenweider P;Jarvelin MR;Lakatta E;Waeber G;Fox CS;Peltonen L;Groop LC;Mooser V;Cupples LA;Thorsteinsdottir U;Boehnke M;Barroso I;Van Duijn C;Dupuis J;Watanabe RM;Stefansson K;McCarthy MI;Wareham NJ;Meigs JB;Abecasis GR
通讯作者：
Abecasis GR
影响因子：
64.8
作者：
Hakonarson, Hakon;Grant, Struan F. A.;Polychronakos, Constantin
通讯作者：
Polychronakos, Constantin
影响因子：
30.8
作者：
Bouatia-Naji, Nabila;Bonnefond, Amelie;Froguel, Philippe
通讯作者：
Froguel, Philippe