AIMS/HYPOTHESIS: The aim was to identify type 2 diabetes susceptibility regions in 250 German families. SUBJECTS AND METHODS: We conducted a genome-wide linkage scan using 439 short tandem repeat polymorphisms at an average resolution of 7.76 +/- 3.80 cM (Marshfield). In an affected-only-design (affected sib pairs), we performed nonparametric multipoint linkage analyses. Conditional analyses were applied where linkage signals were found in the baseline analyses. RESULTS: We identified two loci with nominal evidence for linkage on chromosomes 1p36.13 and 16p12.2 (D1S3669, 37.05 cM, logarithmic odds ratio [LOD] = 1.49, p = 0.004; D16S403, 43.89 cM, LOD = 1.85, p = 0.002). D16S403 crossed the empirically obtained threshold of genome-wide suggestive significance of LOD = 1.51. Positive findings in those regions have been reported by the following other linkage studies on: (1) symptomatic/clinical gall bladder disease with type 2 diabetes in Mexican Americans from the San Antonio Family Diabetes/Gallbladder Study (LOD = 3.7, D1S1597-D1S407, 29.93-33.75 cM); (2) body size-adiposity in another Mexican American population (D1S1597, LOD = 2.53, 29.93 cM); (3) lipid abnormalities (LOD = 3.1, D1S2826-D1S513, 41.92-60.01 cM); and (4) hypertension in Australian sib pairs (LOD = 3.1, D1S2834-D1S2728, 31.02-33.75 cM); as well as (5) a meta-analysis of four European type 2 diabetes-related genome scans (LOD = 1.09, D16S412, 42.81 cM). In linkage analyses conditional on evidence for linkage at D16S403 we identified a LOD increase (Delta LOD) of 1.55 (p = 0.0075) at D17S2180. Similar conditioning on D17S2180 revealed evidence for interaction with D1S3669 (Delta LOD = 1.67, p = 0.0055), D16S403 (Delta LOD = 1.48, p = 0.0091) and another locus on chromosome 1 where several genome scans have reported evidence for linkage ( approximately 200 cM, Delta LOD = 1.60, p = 0.0066). CONCLUSIONS/ INTERPRETATION: Our results and the findings of other studies are consistent with the presence of a locus for a complex metabolic syndrome on chromosome 1p36.13.
AIMS/HYPOTHESIS: The aim was to identify type 2 diabetes susceptibility regions in 250 German families. SUBJECTS AND METHODS: We conducted a genome-wide linkage scan using 439 short tandem repeat polymorphisms at an average resolution of 7.76 +/- 3.80 cM (Marshfield). In an affected-only-design (affected sib pairs), we performed nonparametric multipoint linkage analyses. Conditional analyses were applied where linkage signals were found in the baseline analyses. RESULTS: We identified two loci with nominal evidence for linkage on chromosomes 1p36.13 and 16p12.2 (D1S3669, 37.05 cM, logarithmic odds ratio [LOD] = 1.49, p = 0.004; D16S403, 43.89 cM, LOD = 1.85, p = 0.002). D16S403 crossed the empirically obtained threshold of genome-wide suggestive significance of LOD = 1.51. Positive findings in those regions have been reported by the following other linkage studies on: (1) symptomatic/clinical gall bladder disease with type 2 diabetes in Mexican Americans from the San Antonio Family Diabetes/Gallbladder Study (LOD = 3.7, D1S1597-D1S407, 29.93-33.75 cM); (2) body size-adiposity in another Mexican American population (D1S1597, LOD = 2.53, 29.93 cM); (3) lipid abnormalities (LOD = 3.1, D1S2826-D1S513, 41.92-60.01 cM); and (4) hypertension in Australian sib pairs (LOD = 3.1, D1S2834-D1S2728, 31.02-33.75 cM); as well as (5) a meta-analysis of four European type 2 diabetes-related genome scans (LOD = 1.09, D16S412, 42.81 cM). In linkage analyses conditional on evidence for linkage at D16S403 we identified a LOD increase (Delta LOD) of 1.55 (p = 0.0075) at D17S2180. Similar conditioning on D17S2180 revealed evidence for interaction with D1S3669 (Delta LOD = 1.67, p = 0.0055), D16S403 (Delta LOD = 1.48, p = 0.0091) and another locus on chromosome 1 where several genome scans have reported evidence for linkage ( approximately 200 cM, Delta LOD = 1.60, p = 0.0066). CONCLUSIONS/ INTERPRETATION: Our results and the findings of other studies are consistent with the presence of a locus for a complex metabolic syndrome on chromosome 1p36.13.
Authors: Maggie C Y Ng; Wing-Yee So; Nancy J Cox; Vincent K L Lam; Clive S Cockram; Julian A J H Critchley; Graeme I Bell; Juliana C N Chan Journal: Diabetes Date: 2004-06 Impact factor: 9.461
Authors: Struan F A Grant; Gudmar Thorleifsson; Inga Reynisdottir; Rafn Benediktsson; Andrei Manolescu; Jesus Sainz; Agnar Helgason; Hreinn Stefansson; Valur Emilsson; Anna Helgadottir; Unnur Styrkarsdottir; Kristinn P Magnusson; G Bragi Walters; Ebba Palsdottir; Thorbjorg Jonsdottir; Thorunn Gudmundsdottir; Arnaldur Gylfason; Jona Saemundsdottir; Robert L Wilensky; Muredach P Reilly; Daniel J Rader; Yu Bagger; Claus Christiansen; Vilmundur Gudnason; Gunnar Sigurdsson; Unnur Thorsteinsdottir; Jeffrey R Gulcher; Augustine Kong; Kari Stefansson Journal: Nat Genet Date: 2006-01-15 Impact factor: 38.330
Authors: N Vionnet; El H Hani; S Dupont; S Gallina; S Francke; S Dotte; F De Matos; E Durand; F Leprêtre; C Lecoeur; P Gallina; L Zekiri; C Dina; P Froguel Journal: Am J Hum Genet Date: 2000-11-06 Impact factor: 11.025
Authors: Sobha Puppala; Gerald D Dodd; Sharon Fowler; Rector Arya; Jennifer Schneider; Vidya S Farook; Richard Granato; Thomas D Dyer; Laura Almasy; Christopher P Jenkinson; Andrew K Diehl; Michael P Stern; John Blangero; Ravindranath Duggirala Journal: Am J Hum Genet Date: 2006-01-06 Impact factor: 11.025
Authors: Y Horikawa; N Oda; N J Cox; X Li; M Orho-Melander; M Hara; Y Hinokio; T H Lindner; H Mashima; P E Schwarz; L del Bosque-Plata; Y Horikawa; Y Oda; I Yoshiuchi; S Colilla; K S Polonsky; S Wei; P Concannon; N Iwasaki; J Schulze; L J Baier; C Bogardus; L Groop; E Boerwinkle; C L Hanis; G I Bell Journal: Nat Genet Date: 2000-10 Impact factor: 38.330
Authors: Guowen Cai; Shelley A Cole; Jeanne H Freeland-Graves; Jean W MacCluer; John Blangero; Anthony G Comuzzie Journal: Hum Biol Date: 2004-10 Impact factor: 0.553
Authors: Florence Demenais; Timo Kanninen; Cecilia M Lindgren; Steven Wiltshire; Stéphane Gaget; Candice Dandrieux; Peter Almgren; Marketa Sjögren; Andrew Hattersley; Christian Dina; Tiinamaija Tuomi; Mark I McCarthy; Philippe Froguel; Leif C Groop Journal: Hum Mol Genet Date: 2003-08-01 Impact factor: 6.150
Authors: Alexandra C Finney; Steven D Funk; Jonette M Green; Arif Yurdagul; Mohammad Atif Rana; Rebecca Pistorius; Miriam Henry; Andrew Yurochko; Christopher B Pattillo; James G Traylor; Jin Chen; Matthew D Woolard; Christopher G Kevil; A Wayne Orr Journal: Circulation Date: 2017-05-09 Impact factor: 29.690
Authors: Sebahattin Cirak; Florian von Deimling; Shrikesh Sachdev; Wesley J Errington; Ralf Herrmann; Carsten Bönnemann; Knut Brockmann; Stephan Hinderlich; Tom H Lindner; Alice Steinbrecher; Katrin Hoffmann; Gilbert G Privé; Mark Hannink; Peter Nürnberg; Thomas Voit Journal: Brain Date: 2010-06-16 Impact factor: 13.501
Authors: C Bellis; H C Cox; T D Dyer; J C Charlesworth; K N Begley; S Quinlan; R A Lea; S C Heath; J Blangero; L R Griffiths Journal: Hum Genet Date: 2008-10-31 Impact factor: 4.132