A gene conferring susceptibility to type 2 diabetes in conjunction with obesity is located on chromosome 18p11.
Genome-wide nonparametric linkage analysis of 480 sib-pairs affected with type 2 diabetes revealed linkage to a previously unreported susceptibility locus on chromosome 18p11. This result improved with stringent subphenotyping using age- and sex-adjusted BMI, ultimately reaching a logarithm of odds of 3.82 (allele sharing 0.6654) at a point between markers D18S976 and D18S391 when the most obese 20% of the sample was analyzed. Several genes on chromosome 18 have been suggested as metabolic disease candidates, but none of these colocalize with our linkage result. We conclude that our results provide support for the presence of a currently uncharacterized gene on chromosome 18p, certain alleles of which confer increased susceptibility to type 2 diabetes in conjunction with obesity. We additionally observed moderate evidence for linkage to chromosome 1, near marker D1S3462; chromosome 4, near marker D4S2361; chromosome 5, near marker D5S1505; and chromosome 17, near marker D17S1301.
Millennium Pharmaceuticals, Cambridge, Massachusetts 02139, USA. aparker@mpi.com
A
A
Parker
J
J
Meyer
S
S
Lewitzky
J S
JS
Rennich
G
G
Chan
J D
JD
Thomas
M
M
Orho-Melander
M
M
Lehtovirta
C
C
Forsblom
A
A
Hyrkkö
M
M
Carlsson
C
C
Lindgren
L C
LC
Groop
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008126:Lod Score; D018895:Microsatellite Repeats; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000473:pathology