Abstract
Body mass index (BMI) is used as a measure of fatness. Here we performed a genome-wide scan for genes related to BMI, while allowing for the possible effects of imprinting. We applied a sib pair linkage analysis to a sample of primarily children and young adults by using the Haseman–Elston method, which we modified to model the separate effects of paternally and maternally derived genetic factors. After stratification of sib pairs according to age, a number of regions showing linkage with BMI were identified. Most linkage and imprinting effects were found in children 5–11 years of age. Strongest evidences for linkage in children were found on chromosome 20 at 20p11.2-pter near the marker D20S851 (LODTotal=4.08, P=0.000046) and near the marker D20S482 (LODTotal =3.55, P=0.00016), and Chromosome 16 at 16p13 near the marker ATA41E04 (LODTotal =3.12, P=0.00025), and those loci did not show significant evidence for imprinting. Six regions showing evidence of imprinting were 3p23–p24 (paternal expression), 4q31.1–q32 (maternal expression), 10p14–q11 (paternal expression), and 12p12-pter (paternal expression) in children, and 4q31-qter (paternal expression) and 8p (paternal expression) in adults.
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The study was supported by Grants HL51021, ES09912, and HG02275.
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Appendix A
Appendix A
Interval mapping approach for multipoint parent-specific ibd computation.
Let π1f and π2f be proportion of paternally derived alleles shared ibd by the sibs at two consecutive markers M1 and M2. Let θm,12 be sex-specific (male) recombination fraction between these two flanking markers. Let Mq be a site in between these two flanking markers and let and θm,1 and θm,2 be recombination fractions, based on male map, M1 and Mq and M2 and Mq, respectively. We use and π1f and π2f to obtain πqf, the proportion of paternally derived alleles shared ibd by the sibs at the site Mq. We use the interval mapping approach proposed by Fulker and Cardon22 by using a linear regression equation with π1f and π2f as predictors.
The regression equation we use is
Then, estimators of βπ1f, βπ2f, and α are given by a
and
From Table 2 of Shete and Amos,14 we obtain E(πf) = 1/2, E(πf) = 1/4, and Cov(π1f, π2f) = (1 - 2θm)2 /4. Using these values in above equations, we obtain estimates of β's and α which are given below:
and
For any given site between the two markers M1 and M2, one can convert the distances into recombination fractions using one of the available mapping functions and then obtain the parent-specific multipoint ibd sharing by using equation (A.1). The proportion of maternally derived alleles shared ibd by sibs is similarly obtained.
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Gorlova, O., Amos, C., Wang, N. et al. Genetic linkage and imprinting effects on body mass index in children and young adults. Eur J Hum Genet 11, 425–432 (2003). https://doi.org/10.1038/sj.ejhg.5200979
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DOI: https://doi.org/10.1038/sj.ejhg.5200979
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