A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14.
The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1), the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1 + 2 families (495 updated FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were on chromosomes 6 (maximum logarithm of odds score [MLS] = 2.30 at 95 cM) and 14 (MLS = 1.80 at 57 cM). For the combined FUSION 1 + 2 families, three results were particularly notable: chromosome 11 (MLS = 2.98 at 82 cM), chromosome 14 (MLS = 2.74 at 58 cM), and chromosome 6 (MLS = 2.66 at 96 cM). We obtained smaller FUSION 1 + 2 MLSs on chromosomes X (MLS = 1.27 at 152 cM) and 20p (MLS = 1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1, four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the combined FUSION 1 + 2 sample.
Silander
Kaisa
K
Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA.
Scott
Laura J
LJ
Valle
Timo T
TT
Mohlke
Karen L
KL
Stringham
Heather M
HM
Wiles
Kerry R
KR
Duren
William L
WL
Doheny
Kimberly F
KF
Pugh
Elizabeth W
EW
Chines
Peter
P
Narisu
Narisu
N
White
Peggy P
PP
Fingerlin
Tasha E
TE
Jackson
Anne U
AU
Li
Chun
C
Ghosh
Soumitra
S
Magnuson
Victoria L
VL
Colby
Kimberly
K
Erdos
Michael R
MR
Hill
Jason E
JE
Hollstein
Pablo
P
Humphreys
Kathleen M
KM
Kasad
Roshni A
RA
Lambert
Jessica
J
Lazaridis
Konstantinos N
KN
Lin
George
G
Morales-Mena
Anabelle
A
Patzkowski
Kristin
K
Pfahl
Carrie
C
Porter
Rachel
R
Rha
David
D
Segal
Leonid
L
Suh
Yong D
YD
Tovar
Jason
J
Unni
Arun
A
Welch
Christian
C
Douglas
Julie A
JA
Epstein
Michael P
MP
Hauser
Elizabeth R
ER
Hagopian
William
W
Buchanan
Thomas A
TA
Watanabe
Richard M
RM
Bergman
Richard N
RN
Tuomilehto
Jaakko
J
Collins
Francis S
FS
Boehnke
Michael
M
D017668:Age of Onset; D000368:Aged; D001483:Base Sequence; D001824:Body Constitution; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D017931:DNA Primers; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005190:Family; D005260:Female; D005387:Finland; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D035781:Siblings
D017931:DNA Primers; D005819:Genetic Markers