Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. / Steinthorsdottir, Valgerdur; Thorleifsson, Gudmar; Sulem, Patrick; Helgason, Hannes; Grarup, Niels; Sigurdsson, Asgeir; Helgadottir, Hafdis T; Johannsdottir, Hrefna; Magnusson, Olafur T; Gudjonsson, Sigurjon A; Justesen, Johanne M; Harder, Marie N; Jørgensen, Marit E; Christensen, Cramer; Brandslund, Ivan; Sandbæk, Annelli; Lauritzen, Torsten; Vestergaard, Henrik; Linneberg, Allan; Jørgensen, Torben; Hansen, Torben; Daneshpour, Maryam S; Fallah, Mohammad-Sadegh; Hreidarsson, Astradur B; Sigurdsson, Gunnar; Azizi, Fereidoun; Benediktsson, Rafn; Masson, Gisli; Helgason, Agnar; Kong, Augustine; Gudbjartsson, Daniel F; Pedersen, Oluf; Thorsteinsdottir, Unnur; Stefansson, Kari.
I: Nature Genetics, Bind 46, Nr. 3, 26.01.2014, s. 294-300.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes
AU - Steinthorsdottir, Valgerdur
AU - Thorleifsson, Gudmar
AU - Sulem, Patrick
AU - Helgason, Hannes
AU - Grarup, Niels
AU - Sigurdsson, Asgeir
AU - Helgadottir, Hafdis T
AU - Johannsdottir, Hrefna
AU - Magnusson, Olafur T
AU - Gudjonsson, Sigurjon A
AU - Justesen, Johanne M
AU - Harder, Marie N
AU - Jørgensen, Marit E
AU - Christensen, Cramer
AU - Brandslund, Ivan
AU - Sandbæk, Annelli
AU - Lauritzen, Torsten
AU - Vestergaard, Henrik
AU - Linneberg, Allan
AU - Jørgensen, Torben
AU - Hansen, Torben
AU - Daneshpour, Maryam S
AU - Fallah, Mohammad-Sadegh
AU - Hreidarsson, Astradur B
AU - Sigurdsson, Gunnar
AU - Azizi, Fereidoun
AU - Benediktsson, Rafn
AU - Masson, Gisli
AU - Helgason, Agnar
AU - Kong, Augustine
AU - Gudbjartsson, Daniel F
AU - Pedersen, Oluf
AU - Thorsteinsdottir, Unnur
AU - Stefansson, Kari
PY - 2014/1/26
Y1 - 2014/1/26
N2 - Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114 Icelandic cases and 267,140 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.53, P = 5.0 × 10(-21)) and is correlated with increased CCND2 expression. Notably, this variant is also associated with both greater height and higher body mass index (1.17 cm per allele, P = 5.5 × 10(-12) and 0.56 kg/m(2) per allele, P = 6.5 × 10(-7), respectively). In addition, two missense variants in PAM, encoding p.Asp563Gly (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately higher risk of T2D (OR = 1.23, P = 3.9 × 10(-10) and OR = 1.47, P = 1.7 × 10(-5), respectively), and a rare (0.20%) frameshift variant in PDX1, encoding p.Gly218Alafs*12, associates with high risk of T2D (OR = 2.27, P = 7.3 × 10(-7)).
AB - Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114 Icelandic cases and 267,140 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.53, P = 5.0 × 10(-21)) and is correlated with increased CCND2 expression. Notably, this variant is also associated with both greater height and higher body mass index (1.17 cm per allele, P = 5.5 × 10(-12) and 0.56 kg/m(2) per allele, P = 6.5 × 10(-7), respectively). In addition, two missense variants in PAM, encoding p.Asp563Gly (frequency of 4.98%) and p.Ser539Trp (frequency of 0.65%), confer moderately higher risk of T2D (OR = 1.23, P = 3.9 × 10(-10) and OR = 1.47, P = 1.7 × 10(-5), respectively), and a rare (0.20%) frameshift variant in PDX1, encoding p.Gly218Alafs*12, associates with high risk of T2D (OR = 2.27, P = 7.3 × 10(-7)).
U2 - 10.1038/ng.2882
DO - 10.1038/ng.2882
M3 - Journal article
C2 - 24464100
VL - 46
SP - 294
EP - 300
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 3
ER -
ID: 97378188