Refined association mapping for a quantitative trait: weight in the H19-IGF2-INS-TH region.
Previous analyses have provided evidence for one or more loci affecting body weight in the H19-IGF2-INS-TH region on chromosome 11p15. To identify the location of a possible causal locus or loci we applied association analysis by composite likelihood to a large cohort under the Malecot model for body weight. A random sample of 2731 men in the UK were typed for eleven single nucleotide polymorphisms (SNPs) in IGF2, two SNPs in H19, one SNP in INS and one microsatellite marker in the TH genes. Using F tests appropriate to small marker sets, the superiority of regression over correlation was confirmed. All the evidence for association came from IGF2, with P= 0.007 for height-adjusted weight and P= 0.019 for weight additionally adjusted for smoking and alcohol drinking. Although the estimated point location for the suspected causal variant was close to IGF2 ApaI, the 95% confidence and support intervals covered most of IGF2 but none of the other loci. Identification of the causal SNP or SNPs within IGF2 will require typing of more variants in this region.
Zhang
W
W
Human Genetics Division, University of Southampton, School of Medicine, Duthie Building (MP 808), Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK. wz@soton.ac.uk
Maniatis
N
N
Rodriguez
S
S
Miller
G J
GJ
Day
I N M
IN
Gaunt
T R
TR
Collins
A
A
Morton
N E
NE
D015992:Body Mass Index; D001835:Body Weight / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D015331:Cohort Studies; D006801:Humans; D007335:Insulin-Like Growth Factor II; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011384:Proinsulin / Q000235:genetics; D011506:Proteins / Q000235:genetics; D040641:Quantitative Trait Loci; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics
C094335:H19 long non-coding RNA; C035170:IGF2 protein, human; D011506:Proteins; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D007335:Insulin-Like Growth Factor II; D011384:Proinsulin; D014446:Tyrosine 3-Monooxygenase