A polymorphism in mitochondrial DNA associated with IQ?

In an allelic association study of 100 DNA markers in or near genes of neurological relevance, one restriction fragment length polymorphism (RFLP) yielded significant differences between high- and low-IQ groups in two independent samples. The goal of this article is to describe how we tracked down the specific gene marked by the RFLP and to introduce some current techniques used to apply molecular genetics to complex traits like IQ. The RFLP, EST00083, is a brain-expressed sequence tag site (BESTS) derived from a cDNA hippocampal library. The cDNA clone was shown to involve a chimera between genomic DNA on Chromosome 6 and mitochondrial DNA (mtDNA). The RFLP was localized in the mtDNA rather than the genomic DNA. The RFLP is an MspI restriction site (CCGG) at 15,925 base pairs of the complete mitochondrial genome in a gene that codes for the transfer RNA for threonine. The mitochondrial origin of the EST00083 RFLP explains why the RFLP is maternally transmitted and never yields heterozygotes. Although mtDNA could be associated with IQ, such an unusual result requires further replication

Allelic associations between 100 DNA markers and high versus low IQ

For DNA markers in or near genes of neurological relevance, allelic frequencies were compared for groups of White children high and low in IQ in an attempt to identify specific genes responsible for the substantial heritability of IQ scores. We previously reported results for 60 DNA markers and we now describe results for 40 additional markers. One sample consisted of high- and low-IQ groups with average IQs of 130 (N = 24) and 82 (N = 18), respectively. A replication sample was more extreme, including groups with average IQs of 142 (N = 27) and 59 (N = 17). Three of the 40 markers yielded significant allelic frequency differences between the high- and low-IQ groups in the original sample. In the replication sample, two of these markers (alcohol dehydrogenase 5 and the beta polypeptide of nerve growth factor) yielded results in the same direction but were not significant. The third marker (EST00083), derived from a cDNA hippocampal library, was also significant in the replication sample. As described in another article (Skuder et al., 1995) in this issue, this marker was found to involve mitochondrial DNA (mtDNA) rather than nuclear DNA. The unexpected nature of this marker suggests caution in claiming that the replicated association for EST00083 is indeed a quantitative trait loci (QTL) for IQ until the association receives additional support. This study provides statistical power to detect associations that account for about 2% of the IQ variance in the population. We are currently obtaining samples four times larger that will provide statistical power to detect allelic associations that account for considerably less than 1% of the variance