Simpson gene

Homer and Bart carry the "Simpson gene", which contributes to baldness and laziness.

Effects on different genders
The Simpson gene is only carried by males so Lisa and Maggie don't need to worry; as a matter of fact, it seems that Simpson women in general are very successful so it may be possible that it actually affects women in the opposite way.

However, Marge once claimed that she shared everything with Homer when they were married, including Homer's DNA. Despite her above average intelligence, Lisa has, on occasion, shown some of Homer's traits such as saying "D'oh!" when she encounters trouble or misfortune.

Degree of effect on male Simpsons
While the Simpson gene does affect every male Simpson, it does not always affect them to the same degree. Homer's half brother Herb was able to graduate from Harvard and start up his own successful company. He was still affected by the gene however in small bursts of idiocy (i.e. letting Homer design a car). Homer and Bart have also displayed high levels of intelligence and ability in specified areas (i.e. foreign language, music, bowling) which they could be seen as for. When there was a comet heading towards Springfield and everyone was panicking, Homer theorized that Springfield's polluted atmosphere would prove beneficial as it would burn up the comet and sap its destructive power. After Lisa remarked that Homer was indeed correct, he claimed he was scared by his own accuracy.

Homer Simpson Syndrome
Homer has an unusual condition — "Homer Simpson Syndrome" — where his brain is cushioned by an especially thick layer of fluid, acting as a helmet of sorts. It is unknown whether the Simpson Gene causes Homer Simpson Syndrome, though the males in the Simpson family seem to have a thing for putting pots and pans on their heads and head-butting, suggesting a connection.

Other reasons for Homer's stupidity
Another reason for Homer's stupidity is that a crayon was lodged into his brain when he was six. His IQ without the crayon was 105, placing him in the "average" bracket (90 to about 110, generally). However, he was regarded as a "genius."

Homer has also sustained multiple head injuries throughout the series, which may have contributed to his low IQ.

Homer's obsessive binge drinking may also be a factor. As Homer said once, "Oh Lisa. You and your stories. Bart is a vampire, beer kills brain cells. Now lets go back to that... building... thingy, where our beds and TV... is."

Once, he told Bart about how he wanted a bike when he was a kid but his dad wouldn't let him. So he held his breath until he passed out. He mentioned that the doctors told him he had brain damage.

Homer once went to a military camp for experimental testing to get out of Patty and Selma's visit. The doctors warned it his injections would result in hair loss and lower intelligence. Homer says it was worth it.

He may have also become intellectually challenged due to low self esteem from Abraham Simpson always putting him down. This is reinforced by Homer's statement, that if only Abe hadn't put him down, he might have more of a chance at being successful.

Biological interpretation of the episode
Homer has the defective Simpson gene located on the Y-chromosome. The Simpson 'gene' is actually an allelic anomaly that exerts phenotypic dominance over its counterpart locus on the X-chromosome donated by his mother, regardless of the fact that they are non-homologous. Because it is a dominant allele in this hemizygous condition, the exceptional intelligence that would result from the expression of the allele on the X chromosome is repressed. This repression allows for the expression of only the Simpson 'gene' and causes mental inertia to begin at approximately age 8 and continue to increase in severity until adulthood when it plateaus. Homer's intelligence is therefore naturally below average due to his genetic condition, but his years of work at the nuclear plant have mutated his Y-chromosome and have rendered his Simpson allele inactive. This grants him not only normal intelligence but exceptional intelligence (facilitated by the unblocked allele locus on his X-chromosome inherited from his mother). This intelligence, however, is not expressed because of a crayon lodged in the frontal lobe of his forebrain (a key area of regulation for cognition and behavior) since he was a child (But he could not have been too smart when he was child to put crayons up his nose). It had been removed, revealing his extraordinary intelligence but he insisted it be re-lodged to restore him to normal social status of moron, rather than "nerdy genius".