Loci Contributing to Adult Height and Body Mass Index in African American Families Ascertained for Type 2 Diabetes

Abstract

SummaryHeight and body mass index (BMI) have high heritability in most studies. High BMI and reduced height are well-recognized as important risk factors for a number of cardiovascular diseases. We investigated these phenotypes in African American families originally ascertained for studies of linkage with type 2 diabetes using self-reported height and weight. We conducted a genome wide scan in 221 families containing 580 individuals and 672 relative pairs of African American descent. Estimates of heritability and support for linkage were assessed by genetic variance component analyses using SOLAR software. The estimated heritabilities for height and BMI were 0.43 and 0.64, respectively. We have identified major loci contributing to variation in height on chromosomes 15 (LOD = 2.61 at 35 cM, p = 0.0004), 3 (LOD = 1.82 at 84 cM, p = 0.0029), 8 (LOD = 1.92 at 135 cM, p = 0.0024) and 17 (LOD = 1.70 at 110 cM, p = 0.0044). A broad region on chromosome 4 supported evidence of linkage to variation in BMI, with the highest LOD = 2.66 at 168 cM (p = 0.0005). Two height loci and two BMI loci appear to confirm the existence of quantitative trait loci previously identified by other studies, providing important replicative data to allow further resolution of linkage regions suitable for positional cloning of these cardiovascular disease risk loci.

Comprehensive multi-stage linkage analyses identify a locus for adult height on chromosome 3p in a healthy Caucasian population

“…Hirschhorn et al (2001) identified a height linkage peak on chromosome 3 at 72 cM with a LOD score of 2.3 in a Finnish population. Sale et al (2005) demonstrated linkage of height to chromosome 3 at 84 cM in an African American population with a LOD score of 1.8. Additionally, linkage of spine bone mineral density has been identified on this chromosome in two separate populations at 69 cM (LOD 2.1) and 76 cM (LOD 2.7) (Wilson et al 2003).…”

“…Accurate phenotyping of complex traits is paramount in ensuring meaningful results (Schulze and McMahon 2004). In many published studies, height measures were drawn from questionnaires in which height was self reported (Perola et al 2001;Sale et al 2005;Willemsen et al 2004), or the phenotyping method used is not clearly stated (Deng et al 2002;Hirschhorn et al 2001;Wiltshire et al 2002;Xu et al 2002). The reliability of questionnaires has sometimes been verified (Perola et al 2001), but there is no substitute for measures taken by trained observers on calibrated equipment.…”

“…A further difficulty is that few authors actually present the model used, but simply cite the software and approach used to fit the model, with statements of the form ''variance components models were fitted using SOLAR'' (e.g. Beck et al 2003;Liu et al 2006;Sale et al 2005), which can make it difficult to determine exactly which variance components were included and how covariance was modelled.…”

“…Hirschhorn et al 2001;Xu et al 2002) or accounted for this in segregation analyses . In some cases, simulation studies appear to have assumed random mating (for example Liu et al 2004Liu et al , 2006Sale et al 2005;Wiltshire et al 2002) so results may not be generalisable to real height datasets.…”

Applying Novel Genome-Wide Linkage Strategies to Search for Loci Influencing Type 2 Diabetes and Adult Height in American Samoa

“…These fairly low power estimates suggest that additional chromosome regions not detected in the current study might be of great importance for variation in adult height in the studied population. Since the first genome-wide linkage scans for height were performed in 2001 (Hirschhorn et al 2001;Perola et al 2001), several susceptibility loci for height have been reported [for a recent overview see Perola et al (2007)], but, as for most complex phenotypes, only some have been successfully replicated by further studies (Liu et al 2004(Liu et al , 2006Willemsen et al 2004;Sale et al 2005;Shmulewitz et al 2006). The most promising susceptibility loci for height (Score.Max p = 0.005) detected in our current study of sib-pairs from American Samoa was located on chromosome 9q31 at marker D9S1690.…”